bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer.
Authors: Angioli Roberto , Plotti Francesco , Terranova Corrado , Angelucci Michela , Oronzi Irma , Montera Roberto , Damiani Patrizio , Cafà  Ester Valentina , Guzzo Federica , Montone Eva , Ricciardi Roberto , Aloisi Alessia , Hyseni Entela , Luvero Daniela , Scaletta Giuseppe , Capriglione Stella , Lopez Salvatore , Miranda Andrea , Li Destri Marta , Benedetti Panici Pierluigi 
Published: March 2020

5093 Background: The aim of this study is to evaluate the efficacy, in terms of overall survival and progression free survival, and safety of adjuvant chemotherapy after neoadjuvant chemotherapy followed by radical surgery both in patients with and without node metastases. Methods: Between June 2000 to May 2007, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were elegible for this protocol.All enrolled patients received 3 cycles of platinum-based chemotherapy every 3 weeks according to the scheme cisplatin 100 mg/mq and paclitaxel 175 mg/mq. After neoadjuvant chemotherapy all patients with stable or progression to treatment were excluded from the protocol, all other were submitted classical radical hysterectomy and bilateral systematic pelvic lymph node dissection, and after to adjuvant treatment with 6 cycles of platinum based chemotherapy with cisplatin 100 mg/mq and paclitaxel 175 mg/mq. Results: 110 patients with local advanced cervical cancer received the treatment with neoadjuvant chemotherapy followed by radical surgery and adjuvant chemotherapy.Our study focused on clinical and operative data , in terms of overall survival and disease free survival at 5 and 3 years. 5-year OS of our series was 78% at five years and 86% at 3-years, with encouraging results also in subgroup with and without node mestastases. Conclusions: The adjuvant chemotherapy regimen after neoadjuvant chemotherapy and radical surgery rappresents a valid treatment option for patients with locally advanced cervical cancer without lymph node involvement, both in terms of overall survival than in terms of disease-free interval, the results have also confirmed the validity of this approach in lymph node metastases, with a complication rate lower than the standard radio-chemotherapy regime.
The novel biomarker HE4 versus CA125 in detecting endometrial cancer: A case control prospective study.
Authors: Plotti Francesco , Zullo Marzio Angelo , Angelucci Michela , Oronzi Irma , Damiani Patrizio , Montera Roberto , Dugo Nella , Guzzo Federica , De Oronzo Maria Antonietta , Ricciardi Roberto , Aloisi Alessia , Hyseni Entela , Luvero Daniela , Portuesi Rosa Alba Valentina , Scaletta Giuseppe , Capriglione Stella , Miranda Andrea , Li Destri Marta , Benedetti Panici Pierluigi , Angioli Roberto 
Published: March 2020

5094 Background: In endometrial cancer, there are no markers routinely used in clinical practice. This study prospectively investigates the sensitivity and specificity of new marker HE4 in detection of endometrial cancer. Methods: Serum samples were prospectively obtained 24 hours before surgery from 25 patients with endometrial cancer and from 25 patients with uterine benign pathology, operated from January 2011 to October 2011 at University Campus Bio-Medico of Rome. Preoperative CA125 levels were evaluated by a one-step “sandwich” radioimmunoassay. HE4 levels were determined using the HE4 enzymatic immune assay. The CA125 normal value is considered less than 35 U/mL. Two HE4 cut-off are considered: less than 70 pmol/L and less than 150 pmol/L. The specificity analysis was performed using the parametric T-Test for comparing the HE4 series and the Mann-Whitney test for the CA125 series. The level of statistical significance is set at p < 0.05. Results: The sensitivity of CA125 in detecting endometrial cancer is 16% whereas the sensitivity of HE4 is 48% and 28 % for 70 pmol/L and 150 pmol/L cut-off respectively. The specificity of HE4 is 100% (positive predictive value = 100%, negative predictive value = 65.79% and 58.14% considering the two HE4 cut-off, respectively), whereas the CA125 specificity is 72 % (positive predictive value = 36.36%, negative predictive value = 46.15%) in detection of endometrial cancer. Conclusions: HE4 has a good sensitivity and a specificity of 100% in detection of endometrial cancer and may be useful for detecting early stage endometrial cancer. In particular the HE4 at cut-off of 70 pmol/L yields the best sensitivity and specificity.
Association of adjuvant therapy in early-stage low-risk endometrial cancer with increased mortality: A statewide cancer registry analysis.
Authors: Milam Michael R. , Huang Bin , Moghadamfalahi Mana , Parker Lynn , Metzinger Daniel , Tucker Thomas 
Published: March 2020

5095 Background: National Comprehensive Cancer Network (NCCN) guidelines state that patients with early stage low risk endometrial cancer (defined with 2009 criteria as stage IA endometrioid endometrial cancer) may be managed with observation with consideration of adjuvant therapy.The premise of this study is to review the patterns of care of those patients who received adjuvant therapy and its impact on survival. Methods: This is a retrospective cohort analysis of 1044 women from 2004-2008 in the Kentucky Cancer Registry (KCR) one of the affiliates utilized in the Surveillance, Epidemiology and End Results (SEER) Program database. Inclusion criteria for the patients in this analysis were those women with 2009 Stage IA uterine cancer of endometrioid histology, moderate and well differentiated tumor grade, who received definitive primary surgery. Adjuvant therapy was defined as any postoperative radiotherapy and/or chemotherapy after definitive surgical treatment. Patients with adjuvant therapy after surgery (AT) were compared to those patients who underwent surgery only (SO). Chi-square tests were used to identify associations between type of treatment and clinical/demographic factors. K-M plots and Cox regression models were used to examine survival between the two treatment groups. Results: 5.3% (55/1044) of patients with early stage low risk endometrial cancer were treated with AT compared to 94.7% (989/1044) of SO patients.No statistical differences in mean age, race, tumor size, smoking status, insurance status, lymph node dissection and gynecologic oncology care were found among the AT or SO groups. Five year survival was significantly better in the SO cohort compared to the AT cohort (92% alive at 5 years for SO vs. 66% alive at 5 years; p<0.0001). Controlling for other confounders in the multivariate Cox regression analysis, SO patients had substantially less risk for death compared to the AT groups (HR: 0.21; 95%CI 0.12-0.38; p<0.0001). Conclusions: In this statewide cancer registry analysis, adjuvant therapy after surgery in early stage low risk endometrial cancer patients is uncommon and is associated with an increased risk of mortality.
Neoadjuvant chemotherapy of docetaxel and carboplatin in patients with stage Ib2 to IIb nonsquamous cervix cancer of the uterus.
Authors: Nagao Shoji , Shimada Muneaki , Fujiwara Keiichi , Takeshima Nobuhiro , Takizawa Ken , Shoji Tadahiro , Sugiyama Toru , Yamaguchi Satoshi , Nishimura Ryuichiro , Kigawa Junzo 
Published: March 2020

5103 Background: Non-squamous carcinoma of the uterine cervix has a resistance to radiation therapy and chemotherapy, and this is associated with worse prognosis compared with squamous carcinoma. This is a phase II study to assess an efficacy and safety of neoadjuvant chemotherapy of docetaxel and carboplatin (DC therapy) in patients with stage Ib2 to II non-squamous cervix cancer of the uterus. Methods: Patients with histologically confirmed, stage Ib2-II non-squamous uterine cervix cancer were received DC therapy prior to type III radical hysterectomy. IV doceaxel was administered at 60 mg/m2 followed by IV carboplatin administration based on AUC=6. The treatment was repeated every 21 days for a total of 1 to 3 cycles. Surgery was performed as soon as sufficient response was obtained. Results: Fifty-three women with non-squamous cervical carcinoma (FIGO stage Ib2,15; IIa, 7; IIb, 31) received DC therapy. Median age and tumor size were 49 years old (range: 27-71) and 52mm (range: 10-92), respectively. Fourty of 47 patients (74%) received 2 cycles of chemotherapy. Clinical response occurred in 69.8% of patients (complete response, 5; partial response, 32; stable disease, 15; disease progression, 1), and 96% (52/54) of patients completed the surgery. Incidences of grade 3/4 hematological toxicities were 98% (53/54) for neutrocytopenia, 4% (2/54) for thrombocytopenia, and 9% (5/54) for anemia. Febrile neutropenia was observed in three patients. Observed grade 3/4 non-hematological toxicities included were 5 for nausea, 2 for vomiting, 3 for constipation, 4 for allergic reaction. Median follow-up duration was 860 days with a range of 147- 1635 days. The 2-years progression-free survival rate and 2-years overall survival rate were 63% and 79% in stage IB2, 71% and 86% in stage IIA2, and 67% and 86% in stage IIB, respectively.Twenty patients recurred and twelve patients died. Conclusions: Neoadjuvant chemotherapy using DC therapy was well tolerated and had good response. It seems to be benefical in patients with satge Ib2 to II nonsquamous cervical cancer.
Prognostic significance of high-risk human papilloma virus (HPV), p16, and p53 status in women with vulvar squamous cell carcinoma (VSCC).
Authors: Allo Ghassan , Yap Mei Ling , Cuartero Julie , Mackay Helen , Milosevic Michael , Murphy Joan , Kamel-Reid Suzanne , Pintilie Melania , Clarke Blaise 
Published: March 2020

5105 Background: The incidence of VSCC is increasing. Studies suggest the presence of two histologically and molecularly distinct subsets of VSCC; one contingent on and another independent of HPV infection. However, it is uncertain if HPV status has prognostic significance. HPV oncoproteins can result in degradation of the tumor suppressor p53, cell cycle deregulation and abnormal expression of cyclin dependant kinase inhibitor p16. The aim of this study was to investigate HPV infection, p16 and p53 in relation to clinical parameters in women with VSCC. Methods: Sequential cases of VSCC from patients (pts) treated at Princess Margaret Hospital (PMH) from 2000 to 2008 were reviewed. HPV infection was evaluated by Roche Linear array. A tissue microarray was constructed. p16 and p53 immunohistochemistry was performed. Clinical data was abstracted from medical records and PMH Cancer Database. Survival analysis was performed using Kaplan-Meier curves and log rank test. Results: We identified124 pts with VSCC. HPV was detected in 43/123 (35%) pts (median age 71 ± 16 yrs). HPV16 was the most common serotype (38/43; 88.4%). p16 was expressed in 30/115 (26%) pts and p53 in 59/117 (50.4%) pts. Median age of pts was not different in relation to HPV, p16 and p53 status. Expression of p16 (p<0.0001) and loss of p53 (p=0.007) were associated with HPV infection. Pts with HPV positive tumors were less likely to recur (recurrence rate at 5 years (RR) 12.5% vs 50.3%, p=0.009). HPV positive VSCC were not associated with better 5 yr disease free survival (DFS), 58% vs 31%; p=0.15, or overall survival (OS), 61% vs 61% ; p=0.94. p16 positive tumors had a lower RR at 5 yrs, 23.8% vs 59%, p=0.006 and better 5yr DFS (61% vs 27% ; p=0.009) but not significant for OS (65% vs 59%; p=0.94). Among pts with HPV positive VSCC, OS and DFS were not different between p16 positive and negative VSCC. In the 46 pts treated with radiotherapy, HPV and p16 positive tumors were associated with a lower RR (p=0.004 and 0.005). p53 expression was not prognostic in any pt group. Conclusions: Women with HPV-positiveVSCC have a lower risk of disease recurrence. p16-expressing VSCC are associated with reduced disease recurrence and improved DFS.
Genome-wide association analysis in host characteristics of progression to high-grade cervical intraepithelial neoplasia for women with human papilloma virus infection and normal cytology.
Authors: Lai Chyong-Huey , Chao Angel , Lin Chiao-Yun , Huang Chu-Chun , Su Wen-Hui 
Published: March 2020

5109 Background: Although it is well accepted that persistent human papillomavirus (HPV) is necessary for carcinogenesis of cervical neoplasms, the molecular mechanism for progression is unclear. HPV testing is widely used for cervical cancer screening. The hazard ratio of developing cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) in baseline HPV-positive/normal cytology women is 30-50 fold as compared with HPV-negative/normal cytoloy women. HPV positivity would cause substantial anxiety. It is important to identify a prognostic profile for predicting progression. Methods: We collected blood samples from women aged ≥ 30 years in a population-based nested cohort study enrolling women with HPV infection (n = 871) or HPV-negative (n = 902) with normal cytology in 2004-2009 for prospective follow-up. To identify the host genetic characteristics associated with cervical carcinogenesis, a genome-wide association study (analyzing 530,194 SNPs) was conducted in 23 cases who developed CIN2+ and 62 viral type- and age-matched controls who were HPV-positive at baseline without developing CIN throughout the follow-up period. Results: One SNP with significant P values (rs16969682; P=4.58 x 10-5, OR=5.9, 95% CI=2.52-13.96) located in SEC14-like 1 (SEC14L1) gene localized to chromosome 17 was identified with association between progression to CIN2+ and controls without CIN throughout follow-up. SEC14L1 belongs to the widely-expressed SEC14-superfamily. This superfamily consists of > 500 members that are involved in biological functions including membrane trafficking and phospolipid metabolism. Furthermore, using T-cell based cDNA screening, SEC14L-1a is identified as a regulator of HIV-1 replication. Conclusions: The potential role of SEC14L1 in host-viral interaction will be further elucidated. Additional statistically significant SNPs including rs16969682 will be validated on cases with CIN2+ (n = 250) and normal controls (normal cytology/HPV-negative at baseline without acquisition of HPV or abnormal cytology/histology during follow-up, n = 500).
Nomogram prediction for overall survival of patients diagnosed with cervical cancer.
Authors: Grimm Christoph , Reinthaller Alexander , Hofstetter Gerda , Concin Nicole , Marth Christian , Polterauer Stephan 
Published: March 2020

5111 Background: Cervical cancer is clinically staged based upon the International Federation of Gynecologists and Obstetricians (FIGO) system. FIGO stage is well established as prognostic parameter. It is well known that other additional parameters are useful to estimate overall survival (OS) in patients with cervical cancer. The aim of this multi-center was to create a nomogram to predict OS in patients diagnosed with cervical cancer. Methods: Cervical cancer databases of two large Austrian institutions were analysed. Characteristics known to predict OS were collected. For each patient association between each prognostic parameter and OS was assessed by multivariable modeling. The corresponding 3-year and 5-year OS probabilities were then determined using the nomogram. The constructed nomogram was then validated using the bootstrap correction technique. Results: Mean 5-year OS rates for patients with FIGO stage IA, IB, II, III, and IV were 99.0% (1.0), 88.6% (3.0), 65.8% (5.2), 58.7% (11.0), and 41.5% (14.7), respectively (p<0.001). Mean five-year OS time was 44.2 (30.9) months. Based on the multivariable model FIGO stage, tumor size, age, histologic subtype, lymph node ratio, and parametrial involvement were identified as nomogram parameters. The bootstrap sample corrections provided an estimated concordance probability (interquartile range) of 0.794 (0.779-0.805). Conclusions: Based on 6 easily available parameters a novel nomogram to predict 3-year and 5-year OS of patients diagnosed with cervical cancer was constructed and internally validated. Application of this nomogram allows more accurate and individual prediction of patients’ prognosis.
Progression of genomic signatures in local and metastatic estrogen receptor-positive (ER+) breast cancer: Relevance to palliative treatment.
Authors: Symmans William Fraser , Andreopoulou Eleni , Booser Daniel J. , Hatzis Christos , Wallace Michael J. , Zhang Ya , Gong Yun , Ignatiadis Michail , Sotiriou Christos , Andre Fabrice , Peintinger Florentina , Regitnig Peter , Marth Christian , Desmedt Christine , Loi Sherene , Moulder Stacy L. , Hortobagyi Gabriel N. , Pusztai Lajos , Valero Vicente 
Published: March 2020

515 Background: Biological progression of ER+ breast cancer accelerates clinical progression and resistance to treatments. Methods: One laboratory used Affymetrix U133A gene expression microarrays to profile 588 biopsy samples from patients with ER+ breast cancer: 74 AJCC Stage I, 155 Stage IIA, 105 Stage IIB, 127 Stage III, 127 Stage IV (27 at presentation, 100 relapsed). We evaluated stage dependence of ER [ESR1, PGR, sensitivity to endocrine therapy (SET) index], proliferation [MKI67, AURKA, genomic grade index (GGI)], invasion [PLAU (uPA)], PI3-kinase (PIK3CA-GS), VEGF, genomic subtype [PAM50, 3-gene classifier (ESR1, ERBB2, AURKA)], and housekeeper control genes. Significance was evaluated through ordinal median regression (P < 0.002, for multiple testing) after adjusting for staging method (clinical or pathologic). Exploratory Cox regression analyses of progression-free survival (PFS) and overall survival (OS) were performed when treatment was hormonal therapy (HT, N=58) or chemotherapy (CT, N=27) after biopsy of metastatic ER+ breast cancer (MBC). Results: Stage progression was associated with reduced SET index and increased proliferation (GGI, MKI67, AURKA) and metabolism (GAPDH). These changes occurred between Stages IIB and III, and Stages III and IV. Luminal B and proliferation subtypes were more prevalent in Stage IV and less in Stage I. Interestingly, invasion (PLAU) genes were lower in MBC. Only SET index demonstrated a significant interaction with treatment (HT or CT) for MBC (PFS: p=0.018). SET was predictive of PFS and OS following HT, as a continuous score (PFS: HR=0.69, 95%CI 0.49 to 0.97, p=0.035; OS: HR=0.61, 95%CI 0.40 to 0.94, p=0.025) or dichotomized at median value (PFS: HR=0.43, 95%CI 0.24 to 0.76, p=0.003; OS: HR=0.37, 95%CI 0.18 to 0.77, p=0.006). Genomic subtype was prognostic for PFS irrespective of treatment type. High PIK3CA-GS expression predicted OS in the HT subset. Conclusions: Stage progression was associated with decreased ER-related transcription (SET) and increased proliferation, grade, higher risk subtype, and metabolism. In MBC samples, only SET index was predictive of PFS and OS with palliative hormonal therapy.
Dual effects of metformin on breast cancer proliferation in a randomized trial.
Authors: De Censi Andrea , Pollak Michael N. , Puntoni Matteo , Gandini Sara , Cazzaniga Massimiliano , Pruneri Giancarlo , Serrano Davide , Guerrieri-Gonzaga Aliana , Mora Serena , Gennari Alessandra , Johansson Harriet Ann , Aristarco Valentina , Macis Debora , Bassi Fabio , Luini Alberto , Lazzeroni Matteo , Bonanni Bernardo 
Published: March 2020

519 Background: Metformin lowers breast cancer risk in observational studies in diabetics, but evidence for its clinical activity is scanty. We studied the metformin antiproliferative effect in a pre-surgical study. Since the antidiabetic effect of metformin is heterogeneous according to obesity and insulin resistance (IR), we also determined whether its antiproliferative effect was modified by risk biomarkers. Methods: After tumor biopsy, we randomly allocated 200 non-diabetic women with breast cancer to either metformin, 850 mg/bid (n=100) or placebo (n=100) for 4 wks. The primary endpoint was the post-pretreatment change in Ki-67 between arms. We explored effect modifications by STEPP and tested biomarker thresholds that showed an interaction with treatment on Ki-67. Results: Overall, median (IQR) Ki-67 was 19 (14-31) at baseline and 21 (14-32) after 4 wks and 18 (12-29) at baseline and 20 (13-31) after 4 wks in the metformin and placebo arm, respectively with mean increase of 4.0% (95%CI, -5.6 to 14.4) on metformin versus placebo. Multivariate analyses showed an increase of Ki-67 after 4 wks placebo in the following subgroups: HOMA> IR threshold, IGFBP3> highest quartile, IGFBP1< lowest quintile, IGFratio (IGF1/IGFBP3)< median, CRP> inflection point at STEPP analysis, HER2+ve tumors (versus –ve). Metformin blunted the increase of Ki-67 noted on placebo in these subgroups. Conclusions: Overall, metformin did not affect Ki-67 in most subjects with breast cancer. However, in exploratory analysis we identified subgroups of patients where metformin showed antiproliferative effect. Further studies to a personalized approach are warranted with selection of study populations. [Table: see text]
Impact of expression levels of mRNA HER2 and ESR1 on the pathologic complete remission (pCR) rate after neoadjuvant treatment with anthracycline-taxane containing chemotherapy in combination with trastuzumab in the GeparQuattro trial.
Authors: Huober Jens Bodo , Denkert Carsten , Von Minckwitz Gunter , Prinzler Judith , Kronenwett Ralf , Darb-Esfahani Silvia , Mehta Keyur , Sinn Bruno Valentin , Untch Michael , Loibl Sibylle 
Published: March 2020

523 Background: Recent data suggest that benefit from (neo)adjuvant trastuzumab might be related to expression of HER2 and estrogen receptor (ESR1). We investigated mRNA levels of HER2 and ESR1 in core biopsies in HER2 positive tumors of the GeparQuattro trial and compared it to response to neoadjuvant treatment. Methods: In the GeparQuattro trial 445 HER2+ pts were included based on local testing and received neoadjuvant trastuzumab and chemotherapy (either 4 x EC →4 x docetaxel (D) or 4 x EC → 4 x D/capecitabine (C) or 4 x EC →4x D →4 X C). In 217 available pretherapeutic core biopsies HER2 levels were analysed by IHC, SISH and quantitative RT-PCR using predefined cutoffs; pCR was defined as ypT0is;ypN0. Results: Only 73% of the tumors (158 of 217) were centrally HER2 positive (cHER2+) by IHC/SISH, while 59 tumors (27%) were centrally HER2 negative (cHER2-). As all pts had received neoadjuvant trastuzumab, this gave us the possibility to evaluate response of HER2- tumors to trastuzumab. The pCR rate of cHER2+ tumors was significantly increased (46.8%, p<0.0005) compared to cHER2-, who had a pCR rate of only 20.3%. Similar results were obtained if HER2 positivity was determined by RT-PCR (pCR rate 50% vs. 17.4%, p<0.0005). Assessment of HER2 status by RT-PCR showed a concordance of 86.2% with the IHC/SISH status. In uni- and multivariate logistic regression analysis of cHER2+ cases including continuous HER2 and ESR1 mRNA levels the HER2 mRNA expression was significantly associated with prediction for a pCR in (univ.: OR 1.43, 95% CI 1.11-1.83, p=0.005; multiv.: OR 1.42, 95% CI 1.11-1.83, p=0.006). In the cHER2+ tumors, the pCR rate was similar for ESR1 mRNA positive (47.4%) and ESR1 negative tumors (46.3%). Conclusions: Only pts with cHER2+ tumors independently of the method used have an additional benefit in terms of a pCR from adding trastuzumab to chemotherapy. In cHER2-negative patients the pCR rate is comparable to the pCR rate in the non trastuzumab treated population. Increasing HER2 mRNA levels were associated with a better response to trastuzumab based treatment in cHER2 + tumors.