bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequently deleted genes in ovarian cancer as indicators of platinum response.
Authors: Willis Scooter , Villalobos Victor Manuel , Young Brandon Michael , Sikic Branimir I. , Leyland-Jones Brian 
Published: March 2020

5583 Background: Integrating chromosomal deletions/amplifications with sequencing alterations is increasingly important in the determination of key drivers of outcome in cancer (Leary 2008, Curtis 2012). We introduce a novel computational approach, Gene Set Outcome Analysis, to determine gene signatures constrained to regions with frequent deletion or amplification events in ovarian cancer identified by TCGA. Differential expressions of mRNA from these genes are used as a proxy for loss of function from deletions or amplifications. Methods: Gene signatures from each region were evaluated using log-rank test comparing high and low gene expression groups split by cohort mean. In total, 30,119,708 signatures constrained to 47 deleted and 36 amplified regions were tested for PFS for first line platinum treatment in a random 2/3 split of TCGA ovarian cohort (n=262) resulting in 26,271 gene signatures with p < .001. The remaining 1/3 cohort (n=135) and full cohort (n=397) were used as a replication study where 111 signatures have a p < .01 located in 2 deletion and 1 amplification region. The signature with the lowest p-value from each region that validated in the replication study, were evaluated in GSE9891 (n=179) (Tothill 2008) for PFS when treated with platinum and taxol resulting in gene signatures from 2 deletion regions with p<.05. Results: Greater than mean expression in this gene signature [OXTR, SATB1, WNT7A, SH3BP5, CRBN, ATG7, CRELD1, TMEM43] located at 3p23-p26.2 predicts poor response to platinum chemotherapy in TCGA full ovarian cohort (17.9 vs 14 months p = 1.4E-7) and validates in GSE9891 (19.6 vs 13.3 months p = .014). Using a separate, compact gene signature [CAAP1, LRRC19, IFNA8] located at 9p21.2, samples with lower than mean expression demonstrate increased platinum sensitivity in TCGA full ovarian cohort (12.2 vs 18.2 months p = 1.0E-6) and in GSE9891 (15.5 vs 18.6 p = .055). Conclusions: Response to platinum therapy is an important predictor of survival in high-risk ovarian cancer patients. These signatures arising from common deletion and amplification events in ovarian cancer can anticipate platinum sensitivity and merits further study for use in choosing optimal therapies studying platinum resistance mechanisms.
Pathologic distribution of disease at the time of interval debulking versus primary tumor reduction in women with primary peritoneal, ovarian, or Fallopian tube carcinoma.
Authors: Zaid Tarrik M. , Huang Marilyn , Brown Alaina J. , Balakrishnan Nyla , Mhadgut Hemendra , Pal Navdeep , Wei Caimiao , Broaddus Russell , Bodurka Diane C. , Lu Karen H. , Westin Shannon Neville 
Published: March 2020

5584 Background: The surgical approach for interval debulking after neoadjuvant chemotherapy (NACT) for primary peritoneal, ovarian, or fallopian tube carcinoma has largely been extrapolated from experience with primary tumor reductive surgery (PTRS). It is unknown whether procedures considered mandatory in PTRS, such as hysterectomy, contribute to comparable removal of macroscopic disease in the NACT setting. Our study compared the difference in pathologic distribution of disease at interval debulking surgery versus primary tumor reduction. Methods: After IRB approval, patients who received NACT or PTRS were identified through the tumor registry and surgical database at a single institution from 2008-2012. Involvement of organs at the time of surgery was categorized as either macroscopic, microscopic and no tumor. Statistical analyses included Wilcoxon Mann-Whitney and Fisher’s exact tests. Results: Of the 163 patients identified, 111 (67%) received NACT and 54 (33%) underwent PTRS. Median age was 62 and the majority of patients had stage IIIC high-grade serous carcinoma (91%). Macroscopic ovarian involvement was more common at time of PTRS (92 % vs 63 %, p <0.001). Gross uterine involvement was significantly less in the NACT group compared to PTRS, with the majority of specimens in the NACT group free of disease (Macroscopic 11 % vs 42%, no tumor 62% vs 44 %, p <0.002). However, 27% of the NACT had microscopic uterine serosal disease. Macroscopic large bowel involvement was 50 % in the PTRS vs 26 % in NACT(p<0.005). There was no difference in disease involvement of the small bowel or omentum. Conclusions: The pathologic disease distribution at the time of interval tumor debulking is significantly different from that encountered during primary cytoreductive surgery.. NACT appears to reduce macroscopic large bowel and uterine tumor involvement and may negate the need for hysterectomy and/or large bowel resection at the time of interval debulking to achieve no gross residual.
Regional differences in therapy and clinical management of endometrial cancer: Findings of an international survey by the North-eastern German Society of Gynaecological Oncology (NOGGO).
Authors: Kraetschell Robert W. , Fotopoulou Christina , Dowdy Sean Christopher , Fujiwara Keiichi , Yaegashi Nobuo , Lorusso Domenica , Mahner Sven , Herzog Thomas J. , Casado Herraez Antonio , Vergote Ignace , Miller David S. , Marth Christian , Battista Marco Johannes , Lichtenegger Werner , Sehouli Jalid 
Published: March 2020

5593 Background: We conducted an international survey to evaluate the differences in the systemic, radiotherapeutic and operative management of endometrial cancer (EC) in different regions of the world. Methods: In 2009 avalidated 15-item-questionnaire regarding surgical and adjuvant procedures of EC was sent to all German gynaecological clinics and in 2010 the English adapted questionnaire was set online as well as sent per post in most major gynaecological cancer societies. Results: 316 German institutions and 302 Institutions from 24 countries participated. We combined the different countries into regional groups: Central Europe (CE), southern Europe (SE), Asia and USA/UK. In Asian countries and in CE a lymph node dissection (LND) was performed routinely in 72.8% and in 55.6% of the cases, whereas in the USA/UK and in SE a LND was done mainly in selected cases when specific risk factors such as high-grade or non-endometrioid-histology applied (62.8% and 72.5%) than routinely (p < 0.001). A systematic pelvic and paraaortic LND was performed most frequently in CE 91.0%, in SE 76.9%, in Asia 70.9% and in USA/UK 68.6% (p < 0.001). A systematic LND with the intention of both adequate staging and for therapeutic value was performed in countries of central Europe to 74.6% and in Asia to 67.2%. In USA/UK the LND was seen merely as a staging instrument by 53.5% (p < 0.001). The LND was performed up to renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1 %. A significant difference war found in the treatment for FIGO stage I (high risk factors (high grade, L1,V1)) and stage II disease between the countries: chemotherapy was applied in 84.8% of the participated centers in Asia,42.3% in SE, 21.2% in CE and only 13.6% in USK/UK (p<0.001).Vaginal brachytherapy was indicated as follows: USA/UK 84.1%, CE 78.8%, SE 78.8%, Asia 5.6% (p < 0.001). Conclusions: There is a large variety in the operative therapy and the clinical management of EC in different regions of the world. Future international prospective trials, will be necessary to improve and harmonize the evidence based treatment guidelines for EC- disease.
Early diagnosis program for cervical cancer in Tanzania: The “Vanda Project”.
Authors: Serra Patrizia , Amadori Dino , Nanni Oriana , Gennari Alessandra , Bravaccini Sara , Puccetti Maurizio , Tumino Rosario , Kahima Jackson , Masalu Nestory Andrew ,   African Italian Cooperative Oncology Group (AFRICOG)
Published: March 2020

5594 Background: In Sub-Saharan Africa cervical cancer represents 24% of all cancers and accounts for 23% of all cancer deaths in women. An early diagnosis program for breast and cervical cancer (Vanda Project) is ongoing in Mwanza and the surrounding lake area (12 districts with a population of 14,000,000). The aim of this project was to screen women aged 15-64 years living in the 12 districts. Methods: Women were invited to participate through local media and a mobile unit operating within the districts. A multidisciplinary team including medical oncologists was involved. Interventions consisted in Pap smear, clinical breast examination, breast self-examination training and training of district physicians to perform Pap smear and breast examination. Results: From May to December 2012, 2155 women from the districts of Shinyanga, Bukumbi, Kibara, Serengema and Musoma took part in the program: of these 91 (4%) had clinically evident cervical cancer. Age distribution classes were: < 18 years, 12% ; 18-35, 38%; 36-50, 41%; > 50, 9%. As expected a high stage distribution at diagnosis was observed: 30% stage III and 20% stage IV. Among the women with no clinical evidence of cancer, 408 samples were analyzed by cytology and 4% consisted of inadequate material. Of the remaining 392 samples, 85 (22%) were normal, 216 (55%) were infections (chiefly mycotic), 72 (18%) were precancerous lesions (50% H-SIL according to Bethesda classification) and 19 (5%) were positive for cancer (mainly stages III-IV). Precancerous lesions turned out to be cancer at histology in 44% of cases. 22% of precancerous lesions and 8% of clinically evident cancer were HIV-positive. Conclusions: This experience shows the high feasibility, good compliance and usefulness of a screening program for the early detection of cervical cancer in this high-risk population. [Table: see text]
Disseminated tumor cells in bone marrow of patients with endometrial and cervical cancer.
Authors: Taran Florin-Andrei , Wallwiener Markus , Hartkopf Andreas D. , Walter Christina , Brucker Sara , Rothmund Ralf , Kraemer Bernhard , Wallwiener Diethelm , Fehm Tanja N. 
Published: March 2020

5598 Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients is associated with poor prognosis. Several studies demonstrated that tumor cell dissemination may occur in gynecologic cancer and affect clinical outcome. The aim of our study was to evaluate the incidence of DTC and to assess their prognostic significance in patients with gynecologic malignancies. Methods: Bone marrow aspirates from 623 patients with primary endometrial (331), cervical (228), and vulvar cancer (64) undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between November 2001 and May 2012, were included into the study. Disseminated tumor cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. Results: Disseminated tumor cells were detected in 18% of BM aspirates from patients with gynecological malignancies. Incidences of DTC in endometrial, cervical, and vulvar cancer were 21%, 16% and 16%, respectively. The presence of DTC was associated with a lower tumor grade in endometrial cancer For patients with vulvar cancer, no correlation with established clinicopathological factors was observed. In case of cervical cancer, BM positivity was correlated with International Federation of Gynecology and Obstetrics stage, nodal involvement and the presence of lymphangiosis carcinomatosa. For all analyzed tumor entities, no association between BM status and clinical outcome could be observed. Conclusions: Disseminated tumor cells are a common phenomenon in solid tumors. However, only in cervical cancer DTC postivity was associated with advanced disease. The consequences for DTC positive patients have to be determined.
Conservative management of young women with endometrial adenocarcinoma with grade 2-3 and/or superficial myometrial invasion.
Authors: Park Jeong-Yeol , Kim Dae-Yeon , Kim Tae-Jin , Kim Jae Weon , Kim Jong-Hyeok , Kim Yong-Man , Kim Young-Tak , Bae Duk-Soo , Nam Joo-Hyun 
Published: March 2020

5601 Background: To estimate the oncologic and pregnancy outcomes after progestin treatment of young women with endometrial adenocarcinoma with grade 2–3 and/or superficial myometrial invasion. Methods: Medical records of 48 young women with endometrioid adenocarcinoma of the uterus with grade 2–3 and/or superficial myometrial invasion who were conservatively managed with oral progestin were reviewed. Results: Fourteen patients (29.2%) received daily oral megestrol acetate (median dose, 160 mg/day; range, 40–240 mg/day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose, 500 mg/day; range, 80–1000 mg/day). The median treatment duration was 10 months (range, 3–20 months). Complete responses were observed in 37 patients (77.1%) and the median time to complete response was 17 weeks (range, 9–51 weeks). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with grade 2–3 without myometrial invasion (n=17), patients with grade 1 and superficial myometrial invasion (n=23), and patients with grade 2-3 and superficial myometrial invasion (n=8), respectively (P = 0.731). Their recurrence rates after a median follow-up time of 48 months (range, 7–136 months) were 23.1%, 47.1%, and 71.4%, respectively (P = 0.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy babies. Conclusions: Progestin treatment is safe for patients with grade 2–3 without myometrial invasion and patients with grade 1 and superficial myometrial invasion. However, it should be provided on an individual basis and must be applied cautiously in patients with grade 2–3 and superficial myometrial invasion.
Determination of the activated form of the progesterone receptor (PR) in endometrial cancer (EC).
Authors: Graham Dinny , Bosq Jacques , Caillaud Jean-Michel , Powell Matthew A. , Leblanc Eric , Fujiwara Keiichi , Herzog Thomas J. , Monk Bradley J. , Clarke Christine , Zukiwski Alexander A. , Gilles Erard M. , Coleman Robert L. 
Published: March 2020

5602 Background: Endocrine treatments, in general have limited clinical efficacy in endometrial cancer. Upon ligand binding, PRs in normal tissue form discrete focal subnuclear distribution patterns (FDP), which are associated with DNA transcription. FDP are indicative of functionally activated PRs (APRs), and are observed in EC, independently of menopausal status. The feasibility of using an IHC technique to characterize the PR functional status has previously been reported in breast cancer and the APR phenotype in cell lines correlates with anti-progestin activity. The goal of this study is to determine if APR can be identified in EC and to determine if this IHC technique & APR phenotype could be developed as a companion diagnostic to predict anti-progestin efficacy in patients with EC. Methods: 72 archived primary EC specimens were processed with standard IHC for estrogen receptor (ER), PR & proliferation (Ki67). APR status was determined using commercially available antibodies specific to the A and B isoforms of the PR (PRA and PRB) with standard microscopy at 1000x magnification. Results: 56 (78%) tumors were of endometrioid histology. Endometrioid tumors were ER+ (68%) and PR+ (84%). Two PR nuclear distribution patterns were observed: an aggregated pattern (A) which is indicative of APR and a diffuse or finely granular pattern (D) indicative of an inactivated PR. This resulted in three tumor phenotypes: A cells only, D cells only, and a mix of A + D cells. APR was defined as any tumor with more than 5% A cells. An average of 49% of tumor cells were positive with PRA, 35% were positive for PRB. APR was present with PR A in 41% and with PR B in 47% of the PR+ endometrioid tumors. The APR status, for both PR A and PR B, was independent of PR positivity rate, PR staining intensity score and % Ki67 positive. APRpos phenotype was associated with a lower % ERposstaining. When observable, endometrial stromal and normal cells were PR positive (D pattern). Conclusions: APR can be identified using either PRA or PRB, in ~50 % of the EC samples; there was a pattern consistent with the presence of APR positive cells. The IHC technique to identify APR has the potential to be developed as companion diagnostic as a potential predictor of anti-progestin efficacy.
Comparing intensity modulated radiotherapy and conventional external beam radiotherapy in cervical cancer.
Authors: Gudipudi Deleep Kumar , Alluri Krishnam Raju , De Leon Maria B. , Cardenes Higinia Rosa , Del Priore Giuseppe 
Published: March 2020

5610 Background: To compare Intensity-modulated radiation therapy (IMRT) with conventional external beam radiation therapy (CXRT) regarding morbidity, tumor response, and quality of life (QOL) in cervical cancer patients. Methods: Between 8/2009-2/2010, 50 patients (pts) with age range 20-85, with FIGO Stage IIA- IIIB were prospectively randomized 2:1 to CXRT and IMRT at Indo-American Cancer Institute. Both groups received concurrent chemotherapy (weekly cisplatin 30-40mg/m2) with external beam radiation (EBRT), 50Gy/25fractions followed by intracavitary brachytherapy at 21Gy/3fractions. Complications and QOL were evaluated during treatment and in follow-up with CTC 4.0 and EORTC QLQ-C30, and disease recurrence was based on pelvic exam. Analysis used Chi square(X2) at a significance level of 0.05. Results: Average time to completion was 49 and 48 days in CXRT and IMRT arms (p>.05). Four pts did not complete the treatment in the CXRT. Two months after completion 31/35 (89%) of CXRT and 15/15 (100%) of IMRT had complete response (p>.05). At 5 months, 30/35 (86%) of CXRT, and 14/15 (100%) of IMRT had no loco-regional disease (LRD); 1 IMRT pt died from distant metastasis (DM). At 18 months, 25/35 (72%) in CXRT and 14/15 (93.5%) in IMRT had no LRD or DM. Most common acute side effects in the CXRT were Grade 1 vomiting/cystitis/diarrhea and Grade 2 nausea/skin reactions/proctitis. One pt developed vesicovaginal fistula (VVF) after 50Gy by EBRT. Most common acute side effects in the IMRT were Grade1 nausea/vomiting/cystitis/proctitis/diarrhea. Two pts had grade 3 neutropenia in the 5th week of RT. QOL was better in IMRT (p <.01) based on functional, symptom, single items, and global scales except for pain, insomnia, loss of appetite. Diarrhea, financial problems were worse in the CXRT (p<.05). Chronic complications such as radiation induced proctitis in 5 patients, and sub-acute intestinal obstruction in 2 patients during follow-up period in CXRT vs. IMRT (p < 0.001). Conclusions: IMRT is superior to CXRT with fewer chronic side effects and similar acute side effects and treatment responses. This is the first randomized clinical trial of these treatments in cervical cancer.
Vulvar cancer: Presentation and treatment variation among races.
Authors: Rosin Jennifer , Silberstein Peter T. 
Published: March 2020

5611 Background: Vulvar cancer is the fourth most common gynecologic malignancy. We analyzed variation among races in treatment, histology and stage at presentation using the National Cancer Database (NCDB). Methods: Between 2000 and 2010, 51,157 women from 1338 hospitals across the US were reported to the NCDB with vulvar cancer. Differences were assessed using Chi square analysis. Results: Caucasian patients with vulvar carcinoma in situ received no first course treatment significantly less than African American or Hispanic patients (3% vs 6% and 7%, p<0.05). No treatment for stage I and II vulvar cancer was also significantly less than African American patients (1.4% vs 2.5%, p<0.05). African Americans overall chose radical surgery less often than Caucasians (13% vs 16%, p<0.05), but local tumor excision more (29% vs 24%, p<0.05). African Americans and Hispanics chose no surgery of primary sites significantly more than Caucasians (14% and 15% vs 9%, p<0.05). As expected, squamous cell carcinoma accounts for over 90% of vulvar cancer cases reported. However, Asian-Pacific Islanders had a significantly higher proportion of Extramammary Paget’s disease when compared to Caucasians, African Americans, or Hispanics (20% vs 4.3%, 0.6%, 3.2%. p<0.05). African Americans had the lowest proportion of Extramammary Paget’s compared to any other race for all stages (0.6%, p<0.05). African Americans presented as vulvar carcinoma in situ more often than any other race (33% vs 25-29%, p<0.05). Conclusions: This is the largest study analyzing racial differences in treatment, histology and stage at presentation in women with vulvar cancer. Caucasians were least likely to opt for no first course treatment overall. African Americans were most likely to choose no treatment and, when having surgery, preferred local excision over radical vulvectomy.
A meta-analysis of endocrine therapy trials in early breast cancer (BC) evaluating the impact of obesity: Are aromatase inhibitors (AIs) optimal therapy in obese ER+ BC?
Authors: Pugliano Lina , Zardavas Dimitrios , Paesmans Marianne , Sestak Ivana , Gelber Richard D. , Cuzick Jack M. , Dowsett Mitchell , Awada Ahmad , Piccart-Gebhart Martine J. , De Azambuja Evandro 
Published: March 2020

575 Background: Obesity is an adverse prognostic factor in BC. Mixed results are reported for the relative efficacy of AIs compared to tamoxifen (T) in obese ER+ BC patients. Our purpose was to conduct a meta-analysis of adjuvant randomised trials of AIs vs T assessing the impact of body mass index (BMI). Methods: We identified four studies evaluating BMI and endocrine therapy. Of these, 3 were randomised (non-steroidal AIs vs T) and were evaluable for the aggregation of results for DFS and OS in our meta-analysis. We extracted published data from ATAC, ABCSG-12 and BIG01-98, analyzed according to standard meta-analytic techniques. Results: A total of 11,383 patients were included in our study. BMI>25 is associated with reduced disease free survival (DFS) and a trend towards worse overall survival (OS) (Table 1). A significantly shorter DFS was seen for patients with BMI>25 treated with an AI while a trend was seen for OS. Reduced relative efficacy was seen for DFS for AIs compared to T for BMI<25 (HR=0.78; 95%CI 0.66- 0.91; p=0.002) and a trend for BMI>25 (HR=0.85; 95%CI 0.70- 1.02; p=0.08). The test for interaction was not significant (p=0.48), with similar results for OS for BMI<25 (HR=0.79; 95%CI 0.63-0.9; p=0.009) and BMI>25 (HR=0.98; 95%CI 0.61-1.60; p=0.95). The test for interaction was not significant (p=0.37). Notably, significant heterogeneity in patients treated with anastrozole and a BMI>25 did not allow a comparison between anastrozole and letrozole. Conclusions: BMI>25 has a negative prognostic effect in BC. AIs demonstrate improved outcomes in normal weight BC patients (BMI<25). Obesity was associated with observed relative reduced efficacy of AIs; however, we were not able to detect a significant interaction between BMI and treatment effect. Further analyses into the differing impact of type of AIs on BC outcomes in obese patients are warranted. [Table: see text]