bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race/ethnicity, literacy, and prostate cancer: Initial findings from the COMPARE registry
Authors: Sartor O. , Bennett C. L. , Halabi S. , Kattan M. , Scardino P. 
Published: March 2020

4620 Background: Comprehensive Multicenter Prostate Adenocarcinoma Registry (COMPARE) evaluates variations in initial prostate cancer (PCa) therapy according to race/ethnicity. Similar studies for prostate cancer patients with PSA failure following radiation therapy or radical prostatectomy are unreported. Poor health literacy and African American race are predictive of advanced stage prostate cancers at diagnosis. Methods: COMPARE includes 778 men (62% >70 yr; 80% white and 13% AA) with rising PSA post-localized PCa therapy. Median follow-up post-registry entry is 5 months. Enrollment at 146 sites to date: urology (N = 129), radiation oncology (n = 12), other (n = 5). Most sites are private practice (n = 132) vs academic (n = 14). Health literacy was tested with a 7-item validated word recognition test; scores of ≥4 correlate with ≥6th grade literacy. Variations in therapy, both initial and after PSA failure, were assessed as a function of patient/regional factors. Results: Initial therapy included radical prostatectomy (RP) 44.5%, external beam radiation therapy (EBRT) 30.7%, brachytherapy (BT) 13.1%, other (11.5%). Literacy data are available for 725 men, one fifth had poor literacy skills (<4); higher rates of low literacy were present in AA vs white men (p < 0.05). Significant variations in initial care were associated with poor vs normal literacy skills (brachytherapy: 8% vs 16%; radical prostatectomy: 52% vs 44%, p < 0.05). Watchful waiting was the most common management for PSA failure patients, 82% for men aged ≤70 yr and 77% for men >70 yr. Among prostate cancer patients >70 yr, after adjustment for literacy and Gleason score, African American men were only 41% as likely as whites to undergo watchful waiting (95% CI, 19% to 92%). Conclusions: Poor health literacy is common among men with prostate cancer; these men are more likely to receive radical prostatectomy. With men >70 yr with PSA failure post-radical prostatectomy or post-radiation therapy, African American men were 2.5× more likely than white men to choose therapy (primarily castration) over watchful waiting. Findings from smaller cohorts found that urologic symptoms were the most important factor associated with use of castration versus watchful waiting for PSA failure. No significant financial relationships to disclose.
Utility of prostate specific antigen doubling time (PSA-DT) at the start of androgen independent prostate cancer (AIPC) and immediately before chemotherapy in predicting efficacy of taxane chemotherapy
Authors: Regan M. M. , Daskivich T. J. , Kantoff P. W. , Oh W. K. 
Published: March 2020

4640 Background: PSA-DT has been used to predict efficacy of various treatments for prostate cancer. No study has evaluated the ability of PSA-DT to predict efficacy of taxane chemotherapy, the standard of care for patients with metastatic AIPC. Methods: PSA-DT was retrospectively calculated in 148 AIPC patients treated with taxane chemotherapy. PSA-DT at the start of AIPC (PSA-DT “at AIPC”) was calculated as log 2 divided by the slope of the linear regression of log PSA vs. time, from the first rise above the PSA nadir on androgen deprivation therapy (ADT) until the start of the next treatment. PSA-DT immediately prior to chemotherapy (“pre-chemotherapy” PSA-DT) was calculated similarly, using the three PSA values closest to and no longer than three months before the start of taxane chemotherapy. PSA-DT was divided into tertiles for analysis. Primary outcome was response to chemotherapy, defined as >50% maximum percent reduction in PSA from the start of chemotherapy and was analyzed using logistic regression. Results: PSA-DT at AIPC and pre-chemotherapy PSA-DT could be calculated for 91 and 109 patients, respectively. Rapid pre-chemotherapy PSA-DT (<5 wks) showed a trend towards higher >50% PSA response rates, when compared with intermediate (5–10 wks) and slow PSA-DT (≥10 wks) (74%, 62%, 54%, respectively, P = 0.08 for trend). At androgen independence, rapid PSA-DT (≤ 6 wks) also showed higher >50% PSA response rates than intermediate (6–12 wks) or slow PSA-DT (>12 wks) (81%, 61%, and 62%, respectively) but were not significantly different (P = 0.07, ≤6 vs. >6 wks). Conclusions: Short PSA-DT directly before taxane chemotherapy and also at androgen independence shows a trend towards higher > 50% PSA response rates. PSA-DT at these timepoints will be important to analyze in larger prospective studies. No significant financial relationships to disclose.
The impact of lymphadenectomy in women with endometrioid uterine cancer: A study of 39,396 women
Authors: Karnik Lee N. , Wu H. , Cheung M. K. , Osann K. , Husain A. , Teng N. N. , Berek J. S. , Kapp D. S. , Chan J. K. 
Published: March 2020

5000 Background: To determine the potential benefit of lymphadenectomy (LNX) during surgical staging procedure in women with early and advanced endometrioid uterine cancers. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results program from 1988 to 2001. Data were analyzed by using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of 39,396 women (median age: 65; range 19–102) with endometrioid uterine cancers, 12,333 (31.3%) underwent a surgical staging procedure with LNX. The remainder received a hysterectomy and bilateral salpingo-oophorectomy only. 34,871 (88.5%) were Caucasian, 1,742 (4.4%) were African-American, 1,841 (4.7%) were Asian and 942 (2.4%) were other. The 5-year disease-specific survivals (DSS) were 93.3%, 85.4%, 69.3%, and 38.3% in patients with FIGO stage I-IV diseases, respectively. The 5-year DSS of stage I-IV women who underwent LNX were 95.5%, 90.4%, 73.0%, and 53.3% compared to 96.6%, 82.3%, 61.2%, and 28.2% in those without LNX. Those with stage II (p < 0.001), III (p < 0.001), and IV (p < 0.001) diseases after LNX had significantly better survival; however, the benefit of LNX was not demonstrated in stage I disease. The proportion of stage I patients with grade I histology or tumors limited to the endometrium was significantly higher in those who did not receive LNX compared to those who did (54.8% vs. 34.7%; p < 0.001 for grade I disease; 26.6% vs. 15.9%; p < 0.001 for non-myometrial invasion). In stage I grade 3 endometrioid uterine cancer, patients with LNX had a better 5-year DSS than those without LNX (90.0% vs. 84.97%; p = 0.0001); however, these findings were not seen in grade I (p = 0.26) and grade II (p = 0.14) diseases. In the subset of patients with stage IC grade 3 disease, there was a trend toward an improvement in survival associated with LNX (81.7% vs. 76.5%; p = 0.07). In the overall study group, younger age, African-American race, advanced stage disease, grade 3 histology, and lymphadenectomy. Conclusions: Our data suggest that lymphadenectomy improves the survival of women with stage I grade 3, stage II-IV endometrioid uterine cancers. No significant financial relationships to disclose.
GOG0182-ICON5: 5-arm phase III randomized trial of paclitaxel (P) and carboplatin (C) vs combinations with gemcitabine (G), PEG-lipososomal doxorubicin (D), or topotecan (T) in patients (pts) with advanced-stage epithelial ovarian (EOC) or primary peritoneal (PPC) carcinoma
Authors: Bookman M. A. 
Published: March 2020

5002 Background: P-C is a global standard for treatment of EOC and PPC (GCIG Consensus Conference 2005). Although effective, most patients recur with resistant disease. Agents were selected for new combinations based on clinical activity, interaction with cisplatin in tumor models, and feasibility. Methods: Eligible pts had appropriate initial surgery without other therapy, GOG/WHO PS 0–2, and adequate vital organ function. Pts were stratified by group, diagnosis (EOC vs PPC), stage (III vs IV), macroscopic residual tumor (yes vs no), and intent for interval cytoreduction (yes vs no). An event-triggered interim analysis (IA) of progression-free survival (PFS) was to identify arms for full accrual. The primary endpoint was overall survival (OS), determined by an event-triggered pair-wise comparison to the standard regimen (intent-to-treat), with a 90% chance of detecting a true hazard ratio (HR) of 1.33, limiting type I error to 1.25% (two-tailed) for each comparison. Sample size to be adjusted based on accrual rate and IA. Results: Accrual exceeded 1200/yr. IA for PFS (May 2004) with 1,345 events. Median PFS ranged from 15.4–17.5 m. PFS HRs ranged from 0.94–1.07 with the standard error of each log HR approximately 0.086. Extension was not recommended, and accrual closed at 4312 pts (177 ineligible). Median age 58 yrs; 13% PPC, 14% stage IV, 22% microscopic. 81% completed therapy, 4% progressed, 9% discontinued for toxicity. At least 42 deaths possibly treatment-related (<1%). Expected hematologic toxicity related to regimen intensity. Conclusions: For the regimens evaluated, there is no evidence that adding a third active cytotoxic agent prolongs PFS in EOC. Analysis of OS and impact of stratification factors are in progress. [Table: see text] [Table: see text]
Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer
Authors: Lin N. U. , Carey L. A. , Liu M. C. , Younger J. , Come S. E. , Bullitt E. , Van Den Abbeele A. D. , Li X. , Hochberg F. H. , Winer E. P. 
Published: March 2020

503 Background: One-third of women with HER2+ metastatic breast cancer develop central nervous system (CNS) metastases. This study evaluated the safety and efficacy of lapatinib, an oral inhibitor of EGFR and HER2, in patients with HER2+ brain metastases. Methods: Eligible patients (pts) had HER2+ breast cancer, new or progressive brain metastases, and at least one measurable (LD ≥1.0cm) lesion. Pts received lapatinib 750 mg PO BID. Tumor response was assessed by MRI every 8 wks. FDG-PET scans were performed at baseline, and repeated at wks 1 and 8. The primary endpoint was objective response (CR+PR) in the brain by RECIST. Secondary endpoints included safety, quality-of-life (QOL), and PET changes. Sample size was calculated using a 2-stage design to distinguish objective response of 5% (H0) vs 20% (HA); ≥ 4 objective responses were required to reject the null hypothesis. Results: 39 pts were enrolled, mean age 52 yrs (range 31–76). All pts developed CNS disease on trastuzumab; 38 progressed after prior radiation. Toxicity data are available for 38 pts; the most common AEs were diarrhea (grade 3, 21%), fatigue (grade 3, 16%), and rash (grade 3, 5%). Three pts remain on active treatment. Two pts achieved a PR by RECIST, and remained on study for 158 and 347 days. An additional pt achieved >30% decrease in LD of her CNS lesion but, upon central radiology review, did not meet RECIST criteria for measurable disease and was excluded from analysis of the primary endpoint. Five additional pts achieved SD≥16 wks. Median time to treatment failure was 3.2 mo (95% CI 2.3 to 3.8). Preliminary volumetric analysis of 20/39 pts demonstrates 5 pts with ≥30% volumetric decline in CNS lesions, and an additional 3 pts with 15–30% volumetric decline. Analyses of QOL and correlation of PET with clinical outcomes will be presented. Conclusion: Lapatinib is well-tolerated in this population. Although the study failed to demonstrate the hypothesized level of activity as assessed by RECIST, there is sufficient evidence of clinical effect, albeit preliminary, to suggest that lapatinib can penetrate the CNS. Further investigation of lapatinib in HER2+ CNS disease is warranted and ongoing. Acknowledgements: AVON PFP award; NCI-SPORE in Breast Cancer at DF/HCC(CA89393), UNC(CA58223), Georgetown; ASCO YIA. [Table: see text]
A randomized multicenter phase III trial of topotecan monotherapy versus topotecan + etoposide versus topotecan + gemcitabine for second-line treatment of recurrent ovarian cancer
Authors: Sehouli J. , Sommer H. , Klare P. , Stauch M. , Zeimet A. , Paulenz A. , Steck T. , Riedel H. , Keil E. , Stengel D. , Kuznik A. , Lichtenegger W. 
Published: March 2020

5030 Background: Topotecan combined with etoposide (GINECO 1998) and gemcitabine (NOGGO 2001) proved effective for second-line treatment of recurrent ovarian cancer. It is, however, unclear whether combined treatment improves survival and tumor control compared to topotecan alone. Methods: Women with recurrent ovarian cancer after primary surgery and platinum therapy were enrolled in an open-label randomized phase-III trial at 93 German institutions. Stratifying for treatment-free intervals (TFI) of less or more than 12 months, subjects were centrally allocated to topotecan 1.25 mg/m2/d (TM), topotecan 1.0 mg/m2/d plus oral etoposide 50 mg/d (TE) on day 6–12, or topotecan 0.5 mg/m2/d plus gemcitabine (TG) 800 mg/m2/d1 and 600 mg/m2/d8 every three weeks. Local institutional review boards approved this study, and all patients provided written informed consent. With 145 subjects each arm, this study yielded 90% power to detect a Hazard Ratio (HR) of 0.60 in overall survival (OS) at a two-sided alpha of 0.01. We employed Cox regression for primary endpoint analysis, and addressed progression-free survival (PFS) and toxicity descriptively. Results: Between September 1999 and November 2004, 3036 courses were administered to 505 patients (mean age 60.4 [SD 11.3] years), 208 of whom had a TFI <12 months. Women assigned to TM, TE, and TG received a median of 6.7 (range, 0–10), 6.2 (0–9), and 5.4 (1–42) cycles. Median OS after TM, TE, and TG was 17.8, 17.8, and 15.3 months. Setting TM as the reference, HRs for OS with TE and TG were 1.13 (95% confidence interval [CI] 0.87–1.47) and 1.07 (95% CI 0.80–1.43, p = 0.590). HRs for PFS with TE and TG versus TM were calculated at 0.84 (95% CI 0.66–1.07) each. Subgroup analysis suggested enhanced PFS among subjects with TFI ≥12 months who received TE (HR 0.62, 95% CI 0.42–0.91) or TG (HR 0.68, 95% CI 0.46–1.01) rather than TM. TE produced higher CTC grade 3/4 hematotoxicity than TM or TG, with cumulative incidences of 24.4% (95% CI 20.2–29.0%), 16.0% (95% CI 11.9–20.9%), and 14.7% (10.6–19.5%). Conclusions: This large RCT does not provide evidence that combined treatment performs generally better than topotecan monotherapy in recurrent ovarian cancer. No significant financial relationships to disclose.
A multicentre phase 2 study of carboplatin (C) plus pegylated liposomal doxorubicin (PLD) as first-line chemotherapy for patients (pts) with advanced or recurrent endometrial carcinoma (AEC): The END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer) Group
Authors: Lorusso D. , Pignata S. , Scambia G. , Zagonel V. , Riva N. , Febbraro A. , Pisano C. , Greggi S. , Breda E. , Morabito A. 
Published: March 2020

5041 Background: Anthracyclines and platinum derivates are active drugs for pts with AEC, but new schedules with higher efficacy and better tolerability are needed. A prospective phase 2 study was conducted to describe tolerability and activity of C + PLD in pts with AEC. Methods: Pts with chemo-naïve AEC, PS ≤2, aged less than 75 years and with at least one measurable lesion were eligible. Treatment was C (AUC 5) + PLD (40 mg/m2) on day 1 every 4 weeks, up to 6 cycles. A single-stage design was applied. With objective response as primary endpoint, type I error = 0.05 and II error = 0.10, p0 = 0.20, p1= 0.40, 42 patients were needed, with at least 13 objective responses to define the treatment active. Response was assessed by RECIST and toxicity was coded with NCI-CTC. Results: From November 2002 to July 2005, 42 pts were enrolled at 5 Institutions. Median age was 64 years (31–74). PS was 0/1/2 in 28/13/1 pts, respectively. 62% of pts were stage IV. Out of 40 pts out of treatment, 3 complete (7.5%) and 20 partial responses (50%) have been already observed, for an overall response rate of 57.5% (95% exact CI: 40.9–73.0). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of pts) were g3/4 neutropenia 30%/15%, febrile neutropenia 5%, g3/4 thrombocytopenia pts 17.5%/5%, g3/4 anemia 32.5%/5%, g3 heart rhythm 1 pt, g2 liver toxicity 1pt. Skin toxicity was mild: g1 12.5%, g2 7.5%, g3 5%. Hair loss: complete 1 pt, partial 12.5%. Conclusions: The combination of C and PLD shows a good activity and a favourable toxicity profile in first-line chemotherapy of pts with AEC, deserving further studies in this setting. No significant financial relationships to disclose.
Loss of Apaf-1 expression and resistance to hypoxia-induced apoptosis in cervical cancer
Authors: Leo C. , Horn L. , Rauscher C. , Richter C. E. , Hentschel B. , Hoeckel M. 
Published: March 2020

5046 Background: Clinical observations suggest that intratumoral hypoxia may increase the aggressiveness of tumors through clonal selection of cancer cells that have lost their apoptotic potential. We have shown previously that patients with hypoxic cervical cancers displaying a low apoptosis rate had a significantly worse prognosis compared to all other patients. The aim of this study, therefore, was to investigate the expression of the proapoptotic protein Apaf-1 in cervical cancers and to analyze its relation to intratumoral hypoxia and apoptosis. Methods: 56 patients with cervical cancer (FIGO stage IB to IV) were subjected to pretherapeutical intratumoral pO2 measurement with the Eppendorf electrode after informed written consent was given by each patient. The study was approved by the Ethics Committee of the University of Leipzig. Cervical cancer tissue from these patients was taken by needle core biopsy and analyzed by TUNEL assays as well as by immunohistochemistry with an anti-Apaf-1-antibody. For statistical analysis, Fisher’s exact test was used. Results: Apaf-1 was expressed in 86% of cervical cancers. The median apoptosis rate was 1.0% (range: 0.3– 3.4%). There was no direct correlation between Apaf-1 expression and intratumoral hypoxia. However, in the group of hypoxic cervical cancers (pO2 <10 mmHg) with a low apoptosis rate (<1.0%), 43.8 % (95% CI: 19.8–70.1%) of tumors showed a negative Apaf-1 expression compared to only 2.5% (95% CI: 0.06–13.1%) in non-hypoxic cancers and hypoxic cancers with a high apoptosis rate (p = 0.0003, Fisher’s exact test). Conclusions: While Apaf-1 is expressed in the vast majority of cervical cancers, a significant proportion of tumors with low apoptosis rates despite intratumoral hypoxia showed a loss of Apaf-1 expression. This finding suggests a mechanism by which hypoxic cervical cancers acquire resistance to apoptosis. No significant financial relationships to disclose.
Gene expression signature predicts chemoresponse of microdissected papillary serous ovarian tumors
Authors: Ozbun L. , Bonome T. , Johnson M. E. , Radonovich M. , Pise-Masison C. , Brady J. , Mok S. , Birrer M. E. 
Published: March 2020

5064 Background: The purpose of this study was to identify a predictive gene signature for chemoresponse in patients with advanced stage papillary serous ovarian cancer. Methods: Expression profiling was performed on 50 chemonaive, microdissected advanced stage papillary serous ovarian cancers using Affymetrix Human Genome U133 Plus 2.0 microarrays. Chemoresistance was defined as disease progression while the patients remained on primary chemotherapy. Nine normal human ovarian surface epithelial (HOSE) brushings were also assessed to quantify normal gene expression levels. Validation was performed by quantitative real time PCR using the HOSE isolates and microdissected ovarian tumor samples. Results: A supervised learning algorithm applied to genes differentially expressed between chemosensitive/resistance tumors (p < 0.001) using leave-one-out cross-validation (LOOCV), identified over 2000 genes associated with tumor chemosensitivity. The chemoresponsive gene list was further refined to 576 genes by including only genes used for all LOOCV iterations. An independent gene list was generated comparing expression profiles of chemoresistant tumors to HOSE. The two lists were compared to identify common genes, generating final classifier list of 75 genes that included genes involved in apoptosis, RNA processing, protein ubiquitination, transcription regulation, and other novel genes. We hypothesized genes identified in both data sets would be predictive and biologically relevant. Of these 75 genes, 20 were validated by real-time PCR. Validated genes were ranked by a univariate t-stat value to further resolve the predictor. 4 multivariate predictor algorithms demonstrated the 10 top ranked validated genes maximixed prediction accuracy (compound covariate, 91%; diagonal linear discriminant analysis, 91%; 3-nearest neighbor, 86%; nearest centroid, 95%). The predictive value of these genes will be evaluated on an independent sample set. Conclusions: Gene expression profiling can distinguish between chemosensitive and chemoresistant ovarian cancers. This signature can predict response to therapy and has identified novel biologically and clinically relevant targets. No significant financial relationships to disclose.
Comprehensive analysis integrating both clinicopathological and gene expression data in more than 1,500 samples: Proliferation captured by gene expression grade index appears to be the strongest prognostic factor in breast cancer (BC)
Authors: Sotiriou C. , Wirapati P. , Loi S. , Haibe-Kains B. , Desmedt C. , Tutt A. , Ellis P. , Buyse M. , Delorenzi M. , Piccart M. 
Published: March 2020

507 Background: Although, the development of high-throughput gene expression technologies has allowed the identification of several “molecular signatures” predicting clinical outcome, no attempt has been made yet to perform a comprehensive analysis integrating both clinicopathological, and gene expression data. Here, we aim to elucidate the relationship between clinical parameters and tumor markers, with gene expression patterns and their interaction with prognosis. Methods: We analyzed gene expression and clinical data from several published studies, including more than 1500 BC patients. We developed several gene expression indices associated with different biological stages of disease characterized by the expression of hormone receptors, HER2 amplification, p53 mutation, angiogenesis, tumor invasion and proliferation. Multivariable analyses were used to characterize the dependency patterns between these indices and their impact on survival. Results: Estrogen receptor (ER) and HER2 indices were the most prominent discriminators dichotomizing tumor samples into two main subsets in agreement with the previously proposed BC subtypes. Tumor proliferation, assessed by our previously reported gene expression index (GGI), was the most strongly associated with prognosis (HR 2.29, CI 1.88–2.78, p<0.0001). Almost all ER- and HER2+ tumors were associated with high GGI scores. In contrast, ER+ and HER2- tumors showed a whole range of GGI values. Within the high proliferation subset, ER- and HER2+ indices did not have any prognostic value. Similar results were found with relation to p53 mutation index. Nodal status and tumor size, which essentially measure the duration of disease, retained prognostic value in addition to proliferation. Conclusions: Proliferation captured by the GGI appears to be a key biological factor, downstream of ER, HER2 and p53. Although understanding the upstream factors is important for advancing biological knowledge and therapeutic interventions, GGI seems to be the most important factor predicting clinical outcome in BC and deserves consideration as stratification factor in clinical trials. No significant financial relationships to disclose.