bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial.
Authors: Kehoe Sean , Hook Jane , Nankivell Matthew , Jayson Gordon C. , Kitchener Henry Charles , Lopes Tito , Luesley David , Perren Timothy , Bannoo Selina , Mascarenhas Monica , Dobbs Stephen , Essapen Sharadah , Twigg Jeremy , Herod Jonathan , McCluggage W. Glenn , Parmar Mahesh , Swart Ann Marie 
Published: March 2020

5500 Background: First line treatment of advanced ovarian cancer (OC) is accepted to be primary surgery (PS) followed by adjuvant platinum-based chemotherapy (P-CT). However, the EORTC55971 trial suggested neoadjuvant chemotherapy (NACT) is an alternative, showing increased optimal debulking rates and reduced surgical complications without detriment to survival. CHORUS (CRUK 07/009) is the 2nd phase III randomized controlled trial to investigate timing of initial surgery in OC. Methods: Patients (pts) with clinical FIGO stage III-IV OC (pelvic mass, extrapelvic metastases and CA125/CEA ratio >25) were randomized to standard treatment (PS followed by 6 cycles P-CT) or NACT (3 cycles P-CT either side of surgery). CHORUS was designed to demonstrate non-inferiority of NACT, excluding a 6% absolute detriment in 3yr survival from 50% expected with PS (1-sided alpha 10%). Primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), toxicity and quality of life. Results: 550 women (276 PS, 274 NACT) were randomized from 74 centres (72 UK, 2 NZ) between Mar 2004 and Aug 2010. Baseline characteristics were well balanced: median age 65yrs, median tumor size 80mm, 25% FIGO stage IV, 19% WHO PS 2. Median follow-up was 3yrs, 410 pts have died. Treatment data are summarized in the Table. 3yr survival in the control arm was 32%. Intention to treat analysis showed a median OS of 22.8 months for PS vs 24.5 months for NACT (hazard ratio (HR) 0.87 in favor of NACT, 80% CI 0.76 – 0.98) and median PFS of 10.2 vs 11.7 months (HR 0.91, 0.81 – 1.02). OS results represent a 5% absolute benefit in 3yr survival for NACT to 37% and the upper 80% CI allows us to exclude a survival benefit for PS. Conclusions: NACT was associated with increased optimal debulking, less early mortality and similar survival in this poor prognosis group. CHORUS results are consistent with EORTC55971 and strengthen evidence that NACT is a viable alternative to PS. Clinical trial information: ISRCTN74802813. [Table: see text]
Screening for Lynch syndrome in unselected women with endometrial cancer.
Authors: Ferguson Sarah E. , Aronson Melyssa , Eiriksson Lua R , Mojtahedi Golnessa , Pollett Aaron , Gallinger Steven , Oza Amit M. , Mackay Helen , Bernardini Marcus , Lerner-Ellis Jordan , Clarke Blaise 
Published: March 2020

5508 Background: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch Syndrome (LS) however it is often not recognized in this population. A prospective cohort study comparing family history, immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and tumour morphology to germline mutation status in MMR genes was performed in unselected women with EC to determine which screening strategy was superior in identifying women with LS. Methods: All women with newly diagnosed EC between July 2010 and June 2011 were asked to participate in the prospective screening protocol for LS which included completing an extended family history questionnaire (eFHQ), tumor assessment for LS-associated morphologic features and IHC as well as germline mutation testing. Results: 119 (n = 182, 65%) consented to the study. The median age was 61 (26-91), 96 (81%) stage I, and 42 (35%) had high risk histology. There were 6 (7.4%, n = 81) women that were germline mutation positive (MLH1 N=3; MSH6 n = 2; MSH2 n =1), representing a mutation positive rate of at least 5% in this cohort (6/119). All 3 MLH1 mutation positive women had low grade histology while mutations in MSH2/6 were exclusively found in women with high risk histology. Two of the six mutation positive women were not identified by family history. Mutation positivity was higher in women under age 50 (23%; 5/22) compared to women > age 50 (1%; 1/97)( (p = 0.0008). LS-morphologic features were found in 58 (59%, n = 98) women. The sensitivity, specificity, PPV and NPV of the LS-associated features in predicting LS mutation status was 100%, 42.6%, 7.9% and 100% compared to IHC which was 100%, 76%, 18% and 100% and eFHQ which was 67%, 84%, 27%, 97%. Conclusions: In this unselected population of women with newly diagnosed EC the germline mutation rate for LS was 2-3 times that has previously been reported. Previously described LS-associated morphologic features were not specific to germline mutation status and family history missed one third of women with LS. IHC was the best strategy to identify women with EC who should undergo germline mutation testing.
Prognostic significance of differential expression of angiogenic genes in women with invasive high-grade serous ovarian carcinoma.
Authors: Siamakpour-Reihani Sharareh , Owzar Kouros , Jiang Chen , Turner Taylor , Berchuck Andrew , Marks Jeffrey , Dewhirst Mark , Secord Angeles Alvarez 
Published: March 2020

5509 Background: High-grade serous ovarian carcinoma (HGSC) is an aggressive type of epithelial ovarian cancer associated with numerous genetic alterations and poor survival. Our objective was to identify novel angiogenic biomarkers that are associated with tumor angiogenesis and clinical outcome in women with HGSC. Methods: Between 1988 and 2001, 51 snap frozen samples from women with advanced HGSC were obtained. RNA was extracted and analyzed by the Affymetrix GeneChip U133A array. A panel of 285 probe sets (features) linked to 145 genes involved in angiogenesis were screened. Microvessel density (MVD) counts, surrogates of angiogenesis, were determined using CD31 and CD105, markers of proliferating endothelial cells. The association between mRNA expression levels and overall survival (OS) were assessed using a rank score statistic. The effect size was estimated parametrically as a hazard ratio (HR) under a proportional hazards model. We accounted for multiple testing within the false-discovery rate (FDR) framework using the Storey q-value method. The associations between expression level and OS for the implicated genes were further assessed in a published HGSC cohort from the “The Cancer Genome Atlas” (TCGA) database. Results: A panel of 43 features linked to 31 angiogenic genes were significantly associated with long term OS (FDR q-value (q) < 0.05). In the TCGA cohort, four genes exhibited some level of significance and concordant direction of effect as assessed by HRs: AKT1 (q = 0.018, HR = 0.44; TCGA unadjusted p-value (p) <0.011, HR = 0.81), and CD44 (q < 0.003, HR = 0.48; TCGA p < 0.054, HR = 0.89) were associated with better survival; while EPHB2 (q < 0.009, HR = 8.12; TCGA p < 0.051, HR = 1.23) and ERBB2(q < 0.019, HR = 2.86, TCGA p < 0.055, HR = 1.19) were associated with worse survival. After adjusting for multiple comparisons, CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. Conclusions: Our data demonstrated that mRNA levels of 31 angiogenic genes were associated with OS in advanced HGSC. Among these 4 were externally confirmed using TCGA data. Further evaluation is warranted to verify our preliminary findings.
Ki-67 level in hormone reptor positive breast cancer patients: A retrospective review of 9,061 Korean women.
Authors: Kim Jisun , Han Wonshik , Park Yeon Hee , Jung So Youn , Lee Eun Sook , Ro Jungsil , Moon Hyeong-Gon , Ahn Soo Kyung , Lee Jun Woo , Kim Min Kyoon , Im Seock-Ah , Han Sae-Won , Kim Tae-Yong , Lee Kyung-Hun , Park In Ae , Noh Dong Young 
Published: March 2020

551 Background: Although young age breast cancer represents poor prognosis, no definitive explanation could have been made for the phenomenon. A tumor proliferation marker Ki67 is known to be a marker for both prognosis and prediction for chemotherapy responsiveness, and its level varies widely depending on the breast cancer subtype. This study was aimed to analyze Ki67 in relationship with age in hormone receptor positive breast cancer patients. Methods: We retrospectively reviewed 9061 consecutive cases of hormone receptor positive invasive breast cancer from data base at Seoul National University Hospital (SNUH) (between 2000 and 2012), Samsung Medical Center (SMC) (between 2004 and 2010), and National Cancer Center (NCC) (between 2001 and 2010) in Korea. Patients with estrogen receptor (ER) or progesterone receptor (PR) positive tumors were included irrespective of HER2 amplification. A multicenter data of Ki67 level identified by immunohistochemistry (IHC) and age at diagnosis were analyzed. Patients who underwent neoadjuvant systemic therapy were excluded. Results: Total 6222 cases from SNUH, 976 from SMC and 1863 from NCC were included. The three datasets were analyzed separately due to variable IHC methods in each institute. Mean ages were 49.30 years (range 20-86), 47.75 years (range 22-81) and 45.31 years (range 25-59), and mean Ki67 levels were 4.66% (range 1-100), 22.98% (range 1-97) and 14.58% (range 1-90), at SNUH, SMC, NCC respectively. Ki67 level was inversely proportional with age at diagnosis in all three datasets, and the level was significantly higher for patients <40 years compared to ≥40 years (mean Ki67: 5.97 vs 4.41, p<0.001; 28.60 vs 21.88, p<0.001; 17.01 vs 14.03, p<0.001, respectively). There was an inverse relation with age as well when Ki67 level was categorized into ‘<10% vs ≥10% (p<0.001)’, ‘<20% vs ≥20% (p=0.03)’ and ‘<14% vs ≥14% (p<0.001)’ respectively. Conclusions: Despite the variability of assessing Ki67 expression, Ki67 level was significantly higher in young age hormone receptor positive breast cancer from all three analyses. This could partly explain the poor prognosis and substantial responsiveness to chemotherapy in this age group of patients.
Pazopanib (Paz) monotherapy in Asian women who have not progressed after first-line chemotherapy for advanced ovarian, Fallopian tube, or primary peritoneal carcinoma.
Authors: Zang Rongyu , Wu Lingying , Zhu Jianqing , Kong Beihua , Kim Byoung-Gie , Yao Yuanquing , Yin Rutie , Liu Jihong , Wu Qiang , Ngan Hextan Yuen Sheung , Xie Xing , Wang Kung-Liahng , Li Xiuqin , Yen Ming-Shyen , Wei Lihui , Wang Qiong , Mitrica Ionel , Carpenter Christopher , Zhang Pingkuan 
Published: March 2020

5512 Background: Paz, an oral multikinase inhibitor of VEGF, PDGF and c-Kit has showed activity in advanced ovarian cancer. This study evaluated paz as maintenance therapy in Asian women with advanced ovarian cancer. Methods: Subjects with FIGO stage II, III, or IV ovarian, fallopian tube, or primary peritoneal cancer whose disease had not progressed after debulking surgery and followed by chemotherapy were randomized 1:1 to paz 800 mg once daily or placebo for up to 24 months. Primary endpoint was PFS by RECIST v1.0 based on visit date. If a progression occurred between the 2 scheduled visits (6 mos apart), progression was considered to have occurred at the next scheduled scan date. This minimized potential bias due to any imbalance of visit frequency between the arms. Results: 145 Asian subjects were randomized; 144 were treated. Mean age was 52.9 years. At diagnosis 17% were FIGO stage II, 73% stage III and 10% stage IV. After debulking surgery, 30% (n = 44) had no residual disease and 41% (n = 59) had. 47% (28/59) had residual disease ≤1cm. Prior to randomization, all subjects received median 8 cycles of chemotherapy; all subjects received platinum and taxane. At randomization 81% had ECOG status 0, 97% were disease free and all had normal CA-125. At clinical data cut-off median PFS was 18.1 months in both arms. Because of the small sample size a HR was not calculated but the KM curves indicated a trend in favor of paz from 6 to 18 mos; the curves crossed after 18 mos. The adverse event (AE) profile for paz was similar to previous reports except rates of hypertension and neutropenia were higher. The most frequent AEs (≥ 20%) on the paz arm were hypertension (76%), neutropenia (64%), leucopenia (53%), diarrhea (47%), hair color changes (40%), palm-plantar erythrodysaethesia syndrome (29%), ALT increase (28%), thrombocytopenia (24%), AST increase (22%) and TSH increase (21%). Most of these AEs were Grade 1-2. Conclusions: The results of this study alone cannot confirm the efficacy of paz maintenance treatment in Asian women with ovarian cancer, but should be interpreted in conjunction of AGO-OVAR16 study. Clinical trial information: NCT01227928.
Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: A randomized phase II study of the Sarah Cannon Research Institute.
Authors: Thompson Dana Shelton , Dudley B. Stephens , Bismayer John A. , Gian Victor G. , Merritt William McIver , Whorf Robert C. , Burris Howard A. , Hainsworth John D. 
Published: March 2020

5513 Background: The combination of paclitaxel and carboplatin is the most widely used chemotherapy regimen for patients (pts) with advanced ovarian cancer, producing a median survival of approximately 36 months. Recently, the addition of bevacizumab, an angiogenesis inhibitor, has improved progression-free survival (PFS) when compared to paclitaxel/carboplatin alone. Sorafenib is an oral multi-kinase inhibitor with effects on tumor angiogenesis through inhibition of the VEGF receptor. The purpose of this randomized phase II study was to compare efficacy of paclitaxel/carboplatin with and without sorafenib. Methods: Women with histologically confirmed, maximally debulked, previously untreated stage III/IV epithelial ovarian carcinoma were randomized to receive paclitaxel 175 mg/m2and carboplatin AUC 6 (PC) or PC + sorafenib 400 mg PO BID (S). All patients received 6 cycles, given every 3 weeks; pts receiving PC+S continued single agent sorafenib for 52 weeks total. The primary endpoint was 2-year PFS rate. Results: 85 pts were randomized between 1/07 and 10/11 (PC+S 43; PC 42). Pt characteristics were similar between groups, except that more patients with only CA125 elevation received PC+S (65% vs 43%). Overall, 67 pts (79%) completed 6 cycles of chemotherapy (PC+S 74%; PC 83%). More patients stopped PC+S due to toxicity (14% vs 7%). 22 pts (51%) receiving PC+S began single agent S after 6 cycles PC, and 12 pts (28%) completed 52 weeks of S. There was no difference in the 2-year PFS rates: PC+S 40%, PC 39%. Overall survival comparisons were also similar (p = 0.36). Pts receiving PC+S had more grade 3 rash (33% vs 0%) and hand-foot syndrome (9% vs 0%). Conclusions: The addition of sorafenib did not improve the efficacy of standard first-line PC in pts with stage III/IV ovarian carcinoma, and resulted in additional toxicity. Clinical trial information: NCT00390611.
A randomized placebo-controlled trial of saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian-tube, or primary peritoneal cancer (SaPPrOC).
Authors: McNeish Iain A. , Ledermann Jonathan A. , Webber Lee C. , James Lindsay E. , Kaye Stanley B. , Rustin Gordon J. S. , Hall Geoff , Clamp Andrew , Earl Helena Margaret , Banerjee Susana N. , Kristeleit Rebecca Sophie , Raja Fharat , Feeney Amanda , Lawrence Cheryl , Dawson-Athey Linda , Persic Mojca , Khan Iftekhar 
Published: March 2020

5514 Background: Weekly paclitaxel (wPxl) has activity in platinum-resistant ovarian cancer (PROC). Upregulated Src kinase activity is seen in Pxl-resistant ovarian cancer models. This trial investigated the combination of wPxl and the oral Src inhibitor saracatinib (AZD0530) in PROC. Methods: Patients with PROC (defined as relapse within 6 months of prior platinum chemotherapy, confirmed either by CT scan or symptomatic CA125 rise) were randomised 2:1 to receive four 8 week cycles of wPxl (80mg/m2/week x6 with 2 week break) plus saracatinib (S; 175mg od) or placebo (P) continuously, starting 1 week prior to wPxl, until disease progression. Patients were stratified as <6 months or ≥6 months taxane interval/no prior taxane. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate (RR), duration of response (DoR), time to progression (TTP) and toxicity. Results: 107 patients were randomised during 2011-12, 71 (66.4%) to wPxL+S and 36 (33.6%) to wPxL+P. Taxane interval was <6 months in 23 (22.1%), ≥6 months in 76 (72.4%). 43 (41.0%) had received >2 lines of prior chemotherapy; 78% (wPxL+S) vs 72% (wPxL+P) of patients received ≥1 cycle of wPxl; relative dose intensity was 96% vs 98% for wPxL+S and wPxL+P respectively. The 6-month PFS rate was 29% (wPxL+S) vs 35% (wPxL+P). Median PFS was 3.9 vs 5.3 months (HR 1.04; 95% CI 0.68, 1.59; p=0.86); median OS was 12.7 vs 12.8 months (HR 1.50, 95% CI 0.63, 3.56; p=0.36); RR were 0.0% vs 2.9% (CR) and 29% vs 38.9% (PR) for wPxL+S vs wPxL+P respectively. Median DoR was 5.6 vs 3.6 months; TTP was 3.9 vs 5.5 months (HR 1.10; 95% CI 0.71, 1.72;p=0.67). Grade 3+ Serious Adverse Events were 36.2% vs 30.6%; the most frequent toxicities (any grade) were abdominal pain (4.3%) and febrile neutropenia (4.3%) for wPxL+S, and vomiting (5.6%) for wPxL+P. Conclusions: In this randomised phase II trial, the addition of saracatinib to wPxl did not improve 6-month PFS in patients with PROC. Clinical trial information: NCT01196741.
Effect of metformin on recurrence-free survival and overall survival in diabetic patients affected by advanced ovarian cancer.
Authors: Simonelli Cecilia , Bertolotti Monica , Sabbatini Paul , Berek Jonathan S. , Pfisterer Jacobus , Binaschi Monica , Otranto Isabella , Maggi Carlo Alberto , Scartoni Simona , Capriati Angela 
Published: March 2020

5522^ Background: Metformin, has recently shown some anti-cancer activities in ovarian cancer, both in vitro and in vivo. Methods: Analysis of Recurrence Free Survival (RFS) and Overall Survival (OS) was performed in patients (pts) with diabetes (D) treated with metformin (DMet+) or not (DMet-) enrolled in the MIMOSA trial, a randomized double-blind placebo-controlled international trial of Abagovomab maintenance therapy in 888 pts with advanced ovarian cancer. In the MIMOSA trial, no differences in the RFS and OS were observed between Abagovomab (n = 593) and Placebo arm (n = 295); hence, the present RFS and OS analysis (DMet+ vs DMet-) was run regardless of treatment allocation. A Cox proportional hazards model was used for adjusting the analysis for the predefined prognostic factors: Figo stage (III, IV), tumor size after debulking (residual tumor <1 cm, >1cm); CA125 serum level after 3th cycle (<35U/ml, >35U/ml). In addition, comparison of RFS and OS was done between DMet+and the overall MIMOSA population not exposed to metformin (ALLMet-), and between the overall diabetic pts (ALLD+) and non-diabetic pts (ALLD-). Results: In the ALL population (n = 888), 42 pts were affected by diabetes (ALLD+) divided to DMet+ (n = 27) and DMet- (n = 15), without difference in the prognostic factors distribution. When analysis was done in ALLD+, RFS median time was not reached in the DMet+ group whereas it was 328 days [CI: 30-660] in DMet- group with HR favoring DMet+=0.419 [CI:0.175-1.002]; p = 0.05. Median OS time was also not reached in the DMet+ group whereas it was 786 days [CI:262-NE] in DMet- group with HR=0.295 [CI:0.109-0.803]; p = 0.02. Interestingly HR for RFS time was still in favour of DMet+ group when compared to the ALLMet- (n=861) with HR=0.575 (CI=0.324-1.022); p = 0.06. When ALLD+ were compared with ALLD-(n = 846), no significant differences was detected in RFS and OS time. Conclusions: The present results are the first prospectively analyzed data demonstrating a favourable impact of metformin treatment on RFS and OS in pts affected by advanced ovarian cancer. Clinical trial information: NCT00418574.
GOG0076-GG: A limited access phase II trial of pemetrexed (LY231514) (NSC #698037) in combination with cisplatin (NSC #119875) in the treatment of advanced, persistent, or recurrent carcinoma of the cervix—A Gynecologic Oncology Group study.
Authors: Miller David S. , Blessing John A. , Ramondetta Lois M. , Pham Huyen , Tewari Krishnansu Sujata , Landrum Lisa Michelle , Brown Jubilee , Mannel Robert S. ,   Gynecologic Oncology Group
Published: March 2020

5527 Background: To estimate the antitumor activity of Pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, to determine the effects of this regimen on progression-free survival and overall survival. Methods: Eligible, consenting patients received pemetrexed 500mg/m2 and cisplatin 50 mg/m2 IV repeated every 21 days until disease progression or adverse effects prohibited further therapy. Patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior radiation therapy. Results: From September 2008 to November 2011, 55 patients were enrolled by 5 GOG member institutions. Of those, 49 patients were eligible and assessable. The regimen was well tolerated with 14 (29%) receiving >9 cycles. Common grade >2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial responses). The median response duration was 7 months and survival 12 months. Conclusions: Pemetrexed in combination with cisplatin has demonstrated activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population. Clinical trial information: NCT00691301.