bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated safety result of a large Italian early access program (EAP) with cabazitaxel plus prednisone (CbzP) in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed during or after docetaxel (D) therapy.
Authors: Bracarda Sergio , Di Lorenzo Giuseppe , Gasparro Donatello , Marchetti Paolo , Boccardo Francesco , Martoni Andrea , Carteni Giacomo , Fornarini Giuseppe , Baldazzi Valentina , Dogliotti Luigi , Messina Caterina , Sisani Michele 
Published: March 2020

e15185 Background: A significant percentage of mCRPC pts, who have progressed on D therapy, have a long life expectancy and are candidates for additional treatments. In TROPIC trial pts who progressed during or after D had a statistically significant OS advantage and clinical benefit with CbzP in respect to mitoxantrone plus prednisone (MP). Benefits observed in the TROPIC study supported a global EAP, to allow pts with mCRPC to have an early access to CbzP and provide confirmatory data in daily clinical practice Methods: We report the safety results of the first 90 pts entered into EAP and treated with CbzP, out of 232 pts enrolled by 25 Italian centers between Jan and Aug 2011 Results: Pts characteristics were median age 70 years (≥ 75 years 22.2%); ECOG PS 0-1, 97.8%; median N. of previous D cycles 8 (median cumulative D 675mg/m2); 14.1% received 675 ÷ 900 mg and 40.0% ≥ 900 mg of D. Median time from last D dose to first CbzP dose was 5.29 months including any other chemotherapy treatment.At the time of this analysis 50% of pts had received 4 cycles of CbzP. 33 pts discontinued CbzP mainly due to PD (42.4%), AEs (related/not related, 27.3%), investigator’s (3.0 %) / pts decision (18.2%) and others (9.1%). AEs resulting in CbzP discontinuation (10.0%) are mainly fatigue, pyrexia and haematological disorders. A total of 57 pts were still on treatment. In the 33 discontinued pts, CbzP has been delayed in 24.2% while a dose reduction occurred in 21.2% of pts. AEs of any grade were observed in 81/90 pts. Most common G 3/4 AEs were leukopenia (25.6%), neutropenia (48.9%), anaemia (6.7%), diarrhoea (1.1%), asthenia (3.3%) and fatigue (5.6%). One death occurred during the study period in a heavily pretreated pt who received 33 cycles of D Conclusions: This preliminary safety analysis suggests the good tolerability of cabazitaxel, in terms of haematological as well as non-haematological AEs even in heavily pretreated pts according to the previous experience of Italian Centers in theTROPIC trial. This is remarkable because of the increased similarity of the patient’ populations treated in the EAP and daily clinical practice
Opportunity for all? Socioeconomic disparities in chemotherapy (CT) use for metastatic prostate cancer (mPC).
Authors: Perlroth Daniella , Luna Yesenia L , Thompson Stephen F , Tangirala Muralikrishna , Ng Daniel B , Nicacio Leonardo , Lakdawalla Darius 
Published: March 2020

e15186 Background: CT for mPC is a category 1 recommendation after progression despite hormone therapy (NCCN Clinical Guidelines in Oncology). Having previously documented large regional variations in CT use (Perlroth et al, GU-ASCO, Feb 2-4, 2012), we sought to determine if such disparities exist for patients across socioeconomic status (SES) indicators. Methods: Using Surveillance, Epidemiology, and End Results data linked to Medicare claims, we identified all men diagnosed between 2000 and 2007 with mPC initiated on hormones, excluding patients not continuously enrolled in Medicare Parts A/B or diagnosed with other cancers. We used logistic regression to estimate probability of CT, adjusting for demographic, SES, grade stage and PSA of cancer, and other comorbidities, and tested alternative measures of SES in sensitivity analyses. We report odds ratios (OR) for CT use by socioeconomic status, 95% confidence intervals (CI), and estimates for differences in CT use for high and low SES patients. Results: 7852 patients were in the cohort, mean and median age of 76 and 74 years. 19% advanced to CT, but patients living in regions below the federal poverty level were significantly less likely to do so (OR=0.85, 95% CI: 0.73-0.98). Patients in regions in the bottom quartile of education exhibited OR=0.67 (95% CI: 0.57-0.80) compared with the top quartile. Black race, education, and income factors were not associated with CT use. There were no significant interactions between race and education or income. Median-aged patients residing in the highest-quartile areas versus lowest for education had an estimated 6% higher absolute probability of advancing to CT. After controlling for poverty and education, black race conferred an additional 1% nonsignificant lower probability of advancing to CT over nonblacks. Treatment disparities between groups remained stable during 2000-2007. Conclusions: Education status was the strongest predictor of CT initiation in men with mPC. Poverty and black race also predicted lower CT use. Given that all men in this study were enrolled in Medicare, efforts and research to reduce treatment disparities may need to focus on health system needs serving low socioeconomic communities.
Alternative splicing of Krüppel-like factor 6 (KLF6) enriched in human androgen-deprived prostate cancer (PC).
Authors: Liu XiaoMei , Gomez-Pinillos Alejandro , Loder Charisse , Carrillo-de Santa Pau Enrique , Quiao Rui Fang , Unger Pamela D , Kurek Ralf , Oddoux Carole , Melamed Jonathan , Gallagher Robert E , Mandeli John P , Ferrari Anna C. 
Published: March 2020

e15191 Background: Inactivation of KLF6 by mutations and alternative splicing has been implicated in PC. However, there are significant discrepancies among human PC studies concerning the prevalence and significance of KLF6 mutations, and the prevalence of splice variants (SVs) has not been established. The objective of this study was to assess the prevalence and role of KLF6 splicing in human PC progression. Methods: Human specimens were obtained from the tissue banks of three institutions. Representative epithelium of 74 frozen PC specimens [25 primary hormone-naïve (HN) PCs, 21 primary hormone-deprived (HD) PCs, 6 castrate-resistant metastases] and 22 normal prostates (NPs) were microdissected. KLF6 cDNA was amplified by PCR, cloned and sequenced in both forward and reverse directions and compared to the KLF6 GenBank sequence. The transcriptional activity of KLF6 SVs was evaluated in co-transfection assays with a p21-reporter, and their effect on LNCaP cell growth was determined by MTT assays. Results: Sixteen different SVs were identified: 13 were novel; 14 affected the DNA binding domain (DBD) and were transcriptionally inactive. The incidence of SVs was increased in PC versus NP (75% vs 45%; p=0.01) and in HD-PC versus HN-PC (90% vs 64%; p=0.04) HD-PC were significantly enriched in SVs lacking the DBD. Forced expression of dysfunctional KLF6 SVs increased growth of LNCaP cells in androgen-depleted media. Conclusions: KLF6 SVs lacking p21-reporter transactivation activity occur in NP epithelium but are markedly increased in incidence, variety and level of expression in PC tissues that survive androgen-deprivation. This enrichment may enable resistance to hormone therapy and a proliferative advantage under castrate conditions.
Therapeutic target expression in advanced prostate cancer patients submitted for comprehensive molecular profiling.
Authors: Wright Brian , McGinniss Matthew Jerome , Ghazalpour Anatole , Roberts Christopher , Bender Ryan P , Feldman Rebecca A , Brisbin Lori , Basu Gargi D. 
Published: March 2020

e15209 Background: Approximately 30,000 men die from advanced PCa annually. The prognosis of this disease stresses a need for novel therapeutic and clinical strategies. Methods: We analyzed targeted genes and proteins in 141 patient specimens using IHC (for as many as 29 different biomarkers), FISH for EGFR, ALK, c-Myc, Her2neu and TOP2A, sequencing for BRAF, c-ckit, EGFR, KRAS, and PIK3CA, and RNA expression microarray. Therapeutic associations from the published literature were then assigned based on the differentially expressed biomarkers. Due to amount of tumor tissue present in the specimen, physician test requests and other factors, the number of biomarkers interrogated varied from case to case. Results: Therapeutic associations based on IHC results included:) 92% HER2 negative (potential lack of benefit from HER2 targeted therapy); 85% AR high (potential benefit from anti-androgen therapy); 79% ERCC1 negative (potential benefit from platinum-based therapies); 70% TS negative (potential benefit from fluorouracil),54% PTEN negative (suggesting activation of PIK3CA pathway), 66% RRM1 low (potential benefit from gemcitabine); 64% TOPO2A low (potential lack of benefit from anthracyclines); 44% TOPO1 high (potential benefit from irinotecan) 34% MGMT high (potential lack of benefit from temozolomide); 28% SPARC high (potential benefit from nab-paclitaxel). Potential therapeutic associations based on FISH and Sequencing included: 82% HER2 negative by FISH (potential minimal benefit to HER2 targeted therapy), 13% EGFR positive by FISH and a majority 90% and 81% wild-type for KRAS (exons 2, 3) and BRAF (exons 11, 15), respectively, indicating potential benefit from EGFR targeted therapies. Interestingly, two drug pumps, PGP and MRP1 were 85% negative and 91% positive, respectively. Conclusions: Advanced PCa is an aggressive disease where a one-size-fit-all approach is not effective. Our data confirms that these tumors are heterogeneous at the molecular level and has important therapeutic implications. When developing biomarker enriched clinical trials or advanced treatment planning, a comprehensive molecular profile may provide important insights not otherwise considered.
Endometrial carcinoma in the Baby Boomer generation: Tumor characteristics and clinical outcome.
Authors: Elshaikh Mohamed A. , Shah Mira , Cattaneo II Richard , Mahan Meredith , Buekers Thomas E. 
Published: March 2020

e15512 Background: Baby Boomers (BB) enterring retirement are representing a significant burden on medical resources. The unique lifestyle characteristics engendered by the BB may lead to different endometrial cancer characteristics that bear understanding. We sought to characterize surgically staged BB patients with endometrioid carcinoma and compare the results to pre-Boomers (PB) patients. Methods: After reviewing our database of 1,450 patients with endometrial cancer, we identified 595 patients with 2009 FIGO stage I-II uterine endometrioid carcinoma who were born between 1926 and 1964. Their medical records were reviewed in this IRB-approved study. Patients with non-endometrioid carcinoma and those received preoperative therapy or chemotherapy were excluded. Patients were defined as BB (born 1946-1964) or PB (born in 1926-1945). The two groups were compared regarding patient’s demographics, tumor characteristics and survival. Results: All patients were surgically staged with a minimum of two years follow-up.BB group included 234 patients (39%) and PB with 361 patients (61%).Median follow-up for the study cohort was 72 months. Baby boomers had higher BMI (p=0.027), younger age at diagnosis (p=0.002), lower tumor grade (p=0.002), earlier FIGO stage (p=0.023), higher number of lymph dissected (p=0.008), less lymphovascular space involvement (LVSI) (p=<0.034), and less frequent utilization of adjuvant therapy (p=<0.001). However, there was no statistically significant difference found between the BB and PB in regards to local control, disease-specific survival and overall survival. For the study cohort, FIGO stage and tumor grade were independent predictors of local control and disease-specific survival. As to be expected, there was a trend towards shorter overall survival for the PB patients (p=0.063). Conclusions: Athough tumor characteristics were more favorable in the baby boomers generation, local control and survival endpoints were not statistically different compared to pre boomers. As more baby boomers are diagnosed with endometrial carcinoma, further research is warranted to further elucidate the characteristic differences of endometrial carcinoma, if any, in this generation.
Recurrent ovarian cancer and management of elderly patients: Results of a prospective trial of treosulfan focusing on patient's preference and clinical outcome (NOGGO-Preference-Study).
Authors: Chekerov Radoslav , Braicu Ioana , Harter Philipp , Fuxius Stefan , Mahner Sven , Hanker Lars Christian , Müller Lothar , Klare Peter , Heinrich Georg , Sommer Harald Leo , Fotopoulou Christina , Sehouli Jalid 
Published: March 2020

e15520 Background: There is an increasing interest in the management of elderly patients in oncology. Treosulfan is effective as oral (p.o.) and intravenous (i.v.) formultion for recurrent ovarian carcinoma. Primary aim of this study was to explore the individual preference and compliance of elderly patients (≥ 65 years) for p.o. or i.v.-treosulfan. Secondary aims were to evaluate the ADL-score, toxicity, response and survival. We present the final analysis of patient’s characteristics and treatment choice, compliance of the treatment and toxicities for 123 included patients. Methods: Patients with platinum sensitive and resistant ovarian cancer had free choice of treosulfan i.v. (7000 mg/m² d1, q28d) or p.o. (600 mg/m² d1-28, q56d) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). Indecisive patients were randomized. Toxicity was evaluated according to the NCI-CTC version 2.0. Results: 123 recruited patients received therapy and were able for analysis (median age 72 years, range 65-87). 102 patients chose i.v. and 17 p.o., 3 were randomized to i.v and 1 to p.o. Median ECOG was 1 (n=0-2), and median number of prior chemotherapy-regimens was 3 (n=1-6). Most common hematological toxicities (grade 3/4) were thrombopenia (18.7%), leukopenia (15.4%) and anemia (3.6%). Most frequent non-hematological toxicities (grade 3/4) were abdominal pain (7.3%), fatigue (5.7%) and constipation (4.9%). The median progressive-free survival was 116 days, and the median overall-survival was 239 days. There was no difference in survival and activities of daily life (ADL) score between i.v. and p.o. treosulfan. Conclusions: Although heavily pre-treated most elderly patients with recurrent ovarian cancer (85%) preferred the i.v.-treosulfan administration following their individual preference. Treosulfan therapy was generally well tolerated. There were no differences in the patient’s characteristics, survival and ADL-scores in both groups.
Outcome of pelvic exenteration for recurrent endometrial and cervical cancers.
Authors: Abboud Christelle , Ngo Charlotte , Meria Paul , Fourchotte Virginie , Mariani Pascale , Baranger Bernard , Petrow Peter , Sastre Xavier , Cottu Paul H. , Delarochefordiere Anne , Alran Severine 
Published: March 2020

e15524 Background: Pelvic exenteration has been used as a potentially curative operation in recurrent pelvic malignancies. However, treatment-related morbidity is over 50% in radiated pelves. We evaluated the outcome and the morbidity of pelvic exenteration in women with recurrent cervical and endometrial cancer. Methods: We studied retrospectively all the patients who underwent a pelvic exenteration for recurrent cervical or endometrial cancer in our institution, from January 1999 to November 2011. All medical data were collected. Survival rates were calculated according to Kaplan-Meier method and compared using the log-rank test. Results: twenty-five patients were identified, 17 (68%) had cervical cancer and 8 (32%) endometrial cancer. All patients received a radiation therapy during their initial treatment. All patients had a central pelvic recurrence, in a median time of 30 months [4-384]. 15 patients (60%) had an urinary diversion with incontinent ileoconduit (Bricker). 22 patients (88%) had a complete tumor resection. Severe early complications needing a re-laparotomy occurred in 9 patients (36%) (insufficiencies of intestinal anastomosis, insufficiencies of the ureteral anastomosis and pelvic abscesses). One patient (4%) had a recto-vaginal fistula. Late complications included 1 (4%) vaginal fistula, 1 (4%) intestinal fistula), 2 (8%) intestinal occlusion and 1 (4%) ureteral stenosis. Disease Free and Overall survival rates are better in cervical than in endometrial cancer (median DFS in months 17 [2-145] vs 9.5 [3-21], p= 0.064, median OS in months 20 [2-145] vs 13 [4-42], p=0.019) (table 1). Conclusions: Morbidity of pelvic exenteration remains high. Endometrial cancer is associated with a poorer prognosis. In those patients, the benefit of exenteration should be discussed compared to best supportive care for palliative treatment. [Table: see text]
Weekly ixabepilone with or without concurrent bevacizumab in the treatment of recurrent endometrial cancer.
Authors: Roque Dana Marie , Ratner Elena , Silasi Dan-Arin , Azodi Masoud , Schwartz Peter E. , Rutherford Thomas J. , Santin Alessandro 
Published: March 2020

e15526 Background: Ixabepilone for endometrial cancer has only been evaluated in phase II studies administered at 30-40 mg/m2 q21 days (GOG 129P, GOG 86P). The objective of this study is to describe the institutional experience using a weekly dosing strategy of ixabepilone ± bevacizumab in the treatment of paclitaxel/platinum-resistant recurrent endometrial cancer. Methods: Patients who received weekly ixabepilone (16-20 mg/m2 on days 1, 8, 15 of a 28-day cycle) ± bevacizumab (10 mg/kg on days 1, 15 of a 28-day cycle) off-protocol were identified retrospectively. Results: Thirteen patients were included. Demographic/disease characteristics are provided in Table 1. Median time to first recurrence was 15.9 months (IQR: 9.5-21.66). Patients received a mean of 4.8 ± 1.9 cycles of ixabepilone; treatment is ongoing in 4 patients. A total of 46% of patients demonstrated either a partial response (PR, 8%) or disease stabilization (SD, 38%). PR/SD was associated with a mean decline in CA-125 of 56%. Approximately 50% of patients received concurrent bevacizumab. Of patients who did not receive concurrent bevacizumab, 83% experienced progression and 17% demonstrated SD. Median survival after ixabepilone initiation was 12.7 and 6.9 months in patients treated with and without concurrent bevacizumab, respectively (HR 0.42 [0.09-1.98]). Grade 1/2 hematologic (thrombocytopenia, 15.4%) and gastrointestinal toxicities (emesis/constipation, 7.7%) were observed infrequently. Median overall survival of this cohort was 2.88 years. Conclusions: Ixabepilone shows encouraging activity and promising durability in patients with heavily pre-treated paclitaxel/platinum-resistant recurrent endometrial cancer. Weekly dosing at 16-20mg/m2 on days 1, 8, and 15 ± bevacizumab is well-tolerated. Additional investigation of this regimen and long-term follow-up is warranted. [Table: see text]
Interleukine 10 -592 c/a and interleukine 8 -251 t/a polymorphisms in ovary cancer: New prognostic biomarkers?
Authors: De Mello Ramon Andrade , Marques Dania Sofia , Savva-Bordalo Joana , Gomes Monica , Assis Joana , Coelho Ana , Couto Rosario , Sousa Susana , Afonso Noemia , Medeiros Rui , Pereira Deolinda 
Published: March 2020

e15532 Background: Interleukine (IL) 10 –592C/A and IL8 –251T/A polymorphisms previous showed an important role in cell proliferation, cell migration and angiogenesis. Therefore, we conduct a study in order to assess the role of those genetic polymorphisms as prognostic biomarkers in epithelial ovary cancer (EOC). Methods: Design: Retrospective study from 1996 to 2010. Setting: Histological confirmed EOC patients treated at our institution. Laboratory: Genotyping of IL10–592 C/A and IL8 -251T/A were performed by PCR-RFLP. DNA samples were obtained from patients’ peripheral blood. Statistical analysis: Logistic regression were used to calculate odds ratio (OR) and 95% confidential interval (95% CI). Overall survival (OS) and progression-free-survival (PFS) were performed using Kaplan-Meier analysis. Statistical significance was considered for p < 0.05. Results: It was recruited 156 participants. Median age was 53 (16 – 80) years-old. Genotype frequency distribution for IL8-251 were T/T (50%), T/A (50%) and for IL10–592, C/C (53.8%), C/A (39.7%), A/A (6.4%). These follow genotypes were associated with lymph node, pelvic and peritoneal relapse: IL10–592C/A (OR 0.229, 95% CI: 0.055 – 0.943, p = 0.041) and IL8–251T/A (OR 6.667, 95% CI: 1.359 – 32.701, p = 0.019). In overall, IL8–251T/A genotype had higher OS than IL8-251T/T genotype: 115 versus 95 months, p = 0.010. In clear cell tumors (CCT), IL8–251T/A genotype had less OS than IL8-251T/T genotype: 92 versus 107 months, p = 0.004. To IL10–592 genotypes, OS were 104 (A/A), 107 (C/A), 103 (C/C) months, p = 0.637, and PFS were 9 (A/A), 14 (C/A), 20 (C/C) months, p = 0.057. However, in CCT, PFS for IL10–592 genotypes were 4 (A/A), 56.73 (C/A), 20 (C/C) months, p = 0.023. Conclusions: Our results suggest that IL8–251T/A polymorphism could represent a prognostic biomarker in overall EOC. IL10–592C/A polymorphisms are associated with relapse and PFS mainly in CCT. Nevertheless, furthers prospective studies are warranted in order to assess its role in pharmacogenomics framework.
Palliative external-beam radiotherapy in recurrent ovarian carcinoma.
Authors: Fackrell David Gareth , Anwar Muhammad Suhail , Fernando Indrajit Nalinika , Doyle Yvonne , El-Modir Ahmed 
Published: March 2020

e15534 Background: Up to 80% of patients with advanced ovarian cancer will recur following first-line platinum based chemotherapy. Palliation of focal lesions is often needed to alleviate symptoms. Response rate to second and third-line chemotherapy remain disappointing. The study aim was to characterise the patient population referred for palliative radiotherapy for advanced and recurrent ovarian carcinoma and to assess the effectiveness of radiotherapy in this population. Methods: We retrospectively reviewed the medical records of 94 patients with advanced recurrent ovarian carcinoma referred for palliative radiotherapy between March 1994 and July 2011. The median age of the patients was 62 years (range 33 to 85). One to 16 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 7 cycles). The indications for palliative treatment were: pain (n = 41), mass (n = 32), brain metastases (n = 19), vaginal bleeding (n = 9), rectal bleeding (n = 4), shortness of breath (n = 3), tenesmus (n = 2), skin ulceration (n = 2) and jaundice (n = 1). Some patients received treatment for more than one indication. Sites irradiated included the pelvis (n = 44), brain (n = 19), abdomen (n = 10), bone (n = 5), supraclavicular fossae (n = 4), groins (n = 3), chest (n = 3) and other (n = 6). The median radiotherapy dose was 20 Gy (range: 6 – 50 Gy). The median fraction size was 4 Gy (range: 1.8 – 8 Gy). Results: The overall response rate was 61.7%. Complete palliative response was achieved in 17% of the patients. 27.6% of patients suffered progressive disease during treatment. 10.7% had stable disease. The median duration of palliation was 6 months and closely approximated their survival. The treatment was very well tolerated. Grade 1 or 2 diarrhoea and nausea were the main side effects. Conclusions: External-beam radiotherapy can provide effective and durable palliation of symptoms in patients with recurrent platinum-resistant ovarian carcinoma. The results from palliative radiotherapy are comparable to the published series using second and third-line chemotherapy in the treatment of recurrent focally symptomatic ovarian cancer.