bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degarelix as neoadjuvant hormone therapy in patients with prostate cancer: Results from a phase IIIb randomized, comparative trial versus goserelin plus bicalutamide.
Authors: Mason Malcom , Steidle Christopher P , Deliveliotis Charalambos , Guerif Stephane , Maldonado Xavier , Khoo Vincent , Wiegel Thomas , van der Meulen Egbert , Bergqvist Peter 
Published: March 2020

e15199^ Background: The current approach in patients with high-risk localised or locally advanced PCa is ADT prior to radiotherapy, which improves disease-specific and overall survival vs radiotherapy alone. Whether degarelix, a GnRH antagonist performs comparably with the use of GnRH agonist under flare protection in neoadjuvant settings has not yet been investigated. Methods: Patients with intermediate to high risk PCa were randomised (3:1) to receive either degarelix or goserelin plus bicalutamide (G+B) for 12 wks. The primary endpoint was the percentage reduction from baseline in prostate volume at wk 12 as measured by TRUS. The non-inferiority margin was -10%. Other endpoints included changes in the IPSS, testosterone and PSA. Results: 177 in the degarelix and 62 patients in the G+B arm have completed the trial. 62% and 38% of the patients had localised and locally advanced PCa, respectively. The primary endpoint was successfully met establishing noninferiority between the two treatments in terms of prostate volume reduction at wk 12 (Table). Conclusions: Degarelix was equally effective as prostate shrinking neoadjuvant hormone therapy in patients with intermediate to high risk PCa, but elicited more pronounced LUTS relief compared with G+B after 12 wks of treatment. Possible explanations may involve more pronounced effects on the tumour per se or differences in the action of these drugs on peripheral GnRH receptors expressed in the prostate and the urinary bladder. [Table: see text]
Risk of more advanced cancer at surgery in African American men eligible for active surveillance.
Authors: Salmasi Amirali H , Han Misop , Kim Isaac Yi 
Published: March 2020

e15214 Background: African-American (AA) men have a higher risk for developing prostate cancer (PCa) and dying of PCa compared to Caucasian men. Active surveillance (AS) is an acceptable management for males with low volume and low grade PCa. In Caucasian men who were eligible for AS, the risk of non-organ-confined disease [NOC] at radical prostatectomy (RP) ranges between 7.8 and 10.9% (Kang et al 2011, Mufarrij et al 2010). It is unclear whether AA men with favorable risk PCa can undergo AS safely. We evaluated changes in staging and grading of PCa in a cohort of AA males that met the criteria for AS but underwent RP. Methods: Between 1997 and 2011, 1536 AA men underwent RP at either Johns Hopkins Medical Institutions or Cancer Institute of New Jersey. Pathological characteristics of patients who fulfilled the inclusion criteria under the National Cancer Institute (NCI) AS criteria were examined. NOC (ECE/SV+/LN+) and upgrading (Gleason <7 in biopsy to Gleason >6 in RP) was evaluated. We tried to identify preoperative predictors of more advanced cancer (NOC and/or upgrading). Results: We identified 212 men who underwent RP, eligible for AS based on NCI criteria. Among 212 men, 92 (37.7%) men showed NOC and/or upgrading, defined SV involvement in 5 (2.4%), ECE in 53 (25%), and increased Gleason (<7 to >6) in 69 (32%) men. Pre-operative PSA level (OR 1.2, p < 0.05) and age (OR 1.06, p < 0.01) were significantly associated with more advanced cancer. No significant association was found between BMI, tissue percentage, or positive cores with more advanced cancer. Conclusions: AS in AA with prostate cancer carries higher risk of NOC compared to non-AA population. More stringent AS entrance criteria may be necessary for AA men.
Endometrial cancer recurrence: Adjuvant high-dose rate vaginal brachytherapy (HDR) versus HDR with whole pelvic radiation.
Authors: Villella Jeannine A , Palaia Thomas , Chalas Eva , Patrick Patricia , Haas Jonathan A. 
Published: March 2020

e15504 Background: Investigators hypothesize that patients with endometrioid carcinoma of the endometrium treated with adjuvant high-dose-rate vaginal brachytherapy (HDR) alone vs. HDR with whole pelvic radiation (WPXRT) have similar recurrence patterns. Methods: Patients reated with any adjuvant HDR between March 2005 and January 2011 were included retrospectively. Demographic, pathologic and treatment data was extracted from the medical record. These clinical data were compared among subjects receiving HDR only vs. HDR with 4500 cGy whole pelvic radiation using t-tests, Mann-Whitney tests, and chi-square analyses as appropriate. Results: One hundred eighty-six patients received adjuvant HDR. Fifty eight were excluded from analyses (46 based on non-endometrioid histology; 12 lost to follow-up). Among the sample of 128 subjects, 56 were treated with HDR only vs. 72 with HDR and WPXRT (43.8% vs. 56.2%, respectively). Subjects were similar in age, body mass index, and the existence of medical co morbidities. Of the 72 patients receiving HDR and WPXRT, 28 (38.9) were staged IA-IC, 28 (38.9) were staged as IIA-IIB, 11 (15.4%) were staged as IIIA-IIIC, 1 was staged as IVA-IVB (1.4%) and 4 (5.5%) was unstaged at diagnosis. Complications were similar between the groups. A total of 5 subjects experienced a recurrence, 1 who received HDR only vs. 4 who received HDR and WPXRT (1.8% vs. 5.6%, respectively, p=0.27). The subject treated with HDR was diagnosed with a grade 1 endometrioid carcinoma and had recurrence in the lung. Of the 4 subjects treated with HDR and WPXRT, 3 had recurrence in the vaginal cuff and 1 had recurrence in the peri-aortic lymph nodes. Conclusions: Recurrence was low among all subjects and did not differ among those who received HDR therapy only compared to HDR therapy with whole pelvic radiation. Investigators plan to conduct additional studies with a larger sample size to determine whether a difference in recurrence exists while adjusting for disease stage and total treatment dosage. If such confirmatory evidence is found, HDR brachytherapy alone may be a viable alternative to the additional radiation exposure of WPXRT in treating patients with endometrioid carcinoma of the endometrium.
Combinatorial treatment using CTO with paclitaxel or paclitaxel orotate in sc-implanted human OVCAR-5 ovarian tumor model.
Authors: Maxuitenko Yulia , Gorman Greg , Karmali Rashida A. 
Published: March 2020

e15515 Background: Paclitaxel (PXL) was converted to paclitaxel orotate (PXLO). Different combinations of Carboxyamidotriazole orotate (CTO) and PXL or PXLO were first evaluated in female non-tumored athymic NCr-nu/nu mice to determine the tolerance of the combinations. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor-operated calcium channel-mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, and inhibit FGF-2-induced tyrosine kinase. Methods: The antitumor effect of combinations was tested for: i) PXLO compared to PXL, ii) combinatorial effect of low (342mg/kg/dose) and high (513mg/kg/dose) doses of CTO (Q1Dx14, PO) with low (11.6 and 10mg/kg/inj, Q2Dx3/2 weeks, IV) and high (23.2 and 20mg/kg/inj, Q2Dx3/2 weeks, IV) respectively, doses of PXLO or PXL, against sc-implanted human OVCAR-5 ovarian tumor xenografts. Results: Results obtained in non-tumored mice show high PXLO plus CTO was better tolerated than high PXL plus CTO. In tumor bearing mice, oral CTO at doses of 513 or 342mg/kg/dose Q1Dx14 given alone resulted in slight inhibition of tumor growth, reaching statistical significance only when administered at a low dose (two tumor mass doubling: p=0.036 for 342mg/kg/dose). PXLO at 23.2 and 11.6mg/kg/inj. given alone inhibited tumor growth (p<0.001, 0.029, respectively). PXL at 20 and 10mg/kg/inj inhibited tumor growth (p<0.001 and 0.011, respectively). Since body weight loss was less with the orotate form of PXL, PXLO should be the preferred drug over PXL. Addition of oral CTO 513 or 342mg/kg/dose to PXLO 23.2 or PXL 20mg/kg/inj resulted in comparable tumor inhibition to PXLO or PXL alone. However, combination of PXLO 11.6 and PXL 10mg/kg/inj with CTO 513 or 342mg/kg/dose resulted in tumor inhibition suggesting that a low dose of PXL or PXLO may be combined with CTO to achieve tumor inhibition and to allow the use of the lower doses of PXL to reduce toxicity. Conclusions: Results suggest that PXLO is less toxic than PXL and CTO influences the sensitivity of PXL suggesting a role for combinatorial therapy with low doses of PXL and CTO in this ovarian tumor model.
A regimen of weekly nab-paclitaxel with weekly carboplatin in recurrent ovarian cancer: A retrospective analysis.
Authors: Rauthan Amit , Patil Poonam , Somashekhar S. P. , Zaveri Shabber 
Published: March 2020

e15516 Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.
Engrailed protein: A cancer-specific marker in epithelial ovarian cancer.
Authors: McGrath Sophie , Annels Nicola E. , Madhuri Thumuluru Kavitha , Haagsma Ben , Larbi Emmanuel Douglas , Pandha Hardev S. , Michael Agnieszka 
Published: March 2020

e15517 Background: Ovarian cancer is a common malignancy, accounting for 4% of all cancers and 5% of all cancer deaths in women in the Western world. Engrailed-2 (EN2) is a homeodomain–containing transcription factor that is essential during early development. It is dysregulated in a number of cancers and its presence in urine is diagnostic of prostate cancer. We have investigated its role as a cancer-specific marker in epithelial ovarian cancer (EOC). Methods: Ovarian tumours and normal tissue were collected from patients with epithelial ovarian cancer (EOC) and tested by semi-quantitative RT-PCR as well as by immunohistochemistry. EN2 expression relative to B-actin was calculated using the Livak comparative Ct method (2-DDCt). All slides were scored on a 0-3 scale based on intensity, by two independent assessors. Results: We examined 118 EOC specimens, of which 64 were tested by immunohistochemistry and 54 by RT-PCR. 89 (75.42%) were serous, 18 (15.25%) endometroid, 7 (5.93%) mucinous, and 4 (3.39%) clear cell tumours. Normal ovarian tissue was used as a control. 104 (88.14%) tumours expressed EN2 whilst 14 (11.86%) were negative. Of the EN2 positive tumours examined using immunohistochemistry, 28 (51.85%) strongly expressed the antigen (score of 2-3), whereas 26 (48.15%) were weakly positive (score of 1). Normal tissue did not express EN2 and this difference was statistically significant (p<0.05). There was no correlation with tumour type, grade and stage. EN2 expressing mucinous tumours showed improved overall survival (p=0.0253). There was no correlation for survival or PFS for other histological subtypes. Conclusions: EN2 is a cancer-specific marker in epithelial ovarian cancer. Further work is currently ongoing to evaluate its significance in ascites, blood and urine. We plan to further evaluate its role as a diagnostic biomarker by examining blood, urine, and ascites.
Uterine sarcomas: Analysis of clinicopathologic factors and treatment outcomes—A single institution experience in long-term disease control.
Authors: Go Mylene Sy , Wang Le , Styler Michael , King Stephanie 
Published: March 2020

e15522 Background: Uterine sarcomas behave aggressively and are associated with poor prognosis. Carcinosarcomas was re-classified as more akin to endometrial adenocarcinomas. The objective was to analyze the survival outcomes of all uterine sarcomas treated with various combinations of chemotherapy, radiation, and lymph node dissections. Methods: 60 patients with proven uterine sarcomas were treated at Hahnemann Hospital from 2002-2011. Survival analyses in each treatment group were performed by Kaplan- Meier method Results: Among the 60 women examined, 51% were carcinosarcoma, 25% leiomyosarcoma, 20% endometrial stromal sarcoma, and 4% adenosarcoma. 27% presented with stage I disease, 20% stage II, 13% stage III, and 40% with metastatic disease at diagnosis. One third of the leiomyosarcomas and endometrial stromal sarcomas have advanced disease at diagnosis. Median survival of all patients was 26 months, 20 months for carcinosarcoma, 25 months for high grade endometrial stromal sarcoma, and a trend toward superior overall survival at 73 months for leiomyosarcoma. After surgery, 51% of patients mostly carcinosarcomas received carboplatin and paclitaxel as adjuvant chemotherapy and 66% of leiomyosarcomas received gemcitabine and docetaxel. However, the survival analysis showed no statistically significant benefit in disease progression free survival. On the other hand, 50% of patients were also treated with adjunctive pelvic external beam radiation and 21% received additional vaginal brachytherapy. Our results demonstrated a small but clear survival benefit after pelvic radiation therapy. Pelvic lymphadenectomy was performed in 55% of these patients and lymph node involvement was found in 30% of uterine sarcomas mostly carcinosarcomas. Survival analysis indicated that pelvic lymphadenectomy was associated with significant survival benefit. Conclusions: Size, stage, nodal involvement, and histology are independent prognostic factors. Complete cytoreduction followed by lymph node dissection, and radiation therapy offered a survival advantage than surgery alone. However, the role of adjuvant chemotherapy remains uncertain.
Outcomes of young patients (age younger than 40) with cervical cancer treated with (chemo) radiotherapy: A Japanese multi-institutional study.
Authors: Ariga Takuro , Niibe Yuzuru , Toita Takafumi , Kazumoto Tomoko , Eto Hidehiro , Suzuki Osamu , Kinoshita Rumiko , Tsujino Kayoko , Takemoto Mitsuhiro , Kodaira Takeshi , Yamashita Hideomi , Hayakawa Kazushige 
Published: March 2020

e15533 Background: To analyze treatment outcomes of young patients (age: <40 years) with uterine cervical cancer treated with definitive (chemo) radiotherapy in Japanese institutions. Methods: The records of 118 patients (age: <40 years) with cervical cancer were reviewed retrospectively. The median age was 35 years (range: 24-39 years). Clinical FIGO stages were as follows: Stages 1b1/1b2/1b/2a/2b/3a/3b/4a/unknown in 6/9/2/6/40/2/49/3/1 patients, respectively. Median maximum tumor diameter was 5.5 cm (range: 2-9.2 cm). Forty-six patients (39%) had enlarged pelvic nodes (>10 mm in the shortest diameter). One hundred five patients had squamous cell carcinoma, and 13 patients had non-squamous cell carcinoma. Definitive radiotherapy consisted of high-dose rate intracavitary brachytherapy and whole-pelvis external beam radiation therapy. The cumulative linear quadratic equivalent dose (EQD2) was 64 Gy (range: 30-80 Gy) prescribed at point A. Concurrent chemotherapy was delivered in 95 patients (81%). Results: Within a median follow-up time of 35 months, 44 patients developed recurrence. Thirty-nine patients (33%) had pelvic recurrence only, four patients (3%) had distant metastasis only, and one patient had both pelvic and distant metastasis. The 5-year overall survival rate (OS) and local control rate (LC) of all patients were 62 % and 64 %, respectively. The 5-year OS for patients with disease stages 1b1/1b2/2a/2b/3/4a were 80%/89 %/100 %/75 %/40 %/0 %, respectively. The 5-year LC for patients with disease stages 1b1/1b2/2a/2b/3/4a were 100%/78%/50%/75%/51%/0%, respectively. Twelve patients (10%) suffered grade 3 or higher late radiation morbidity. Conclusions: Our results suggest that young patients (age: <40 years) with cervical cancer, especially in locally advanced stages (stage III and IVA), might have a worse prognosis than older patients when treated with definitive (chemo) radiotherapy.
Small cell carcinoma of the female genital tract: A single institution experience.
Authors: El-Gehani Faraj , Sun Julia , Kamal Muna , Pertschy Danielle , Joseph Kurian , Tonkin Katia , Ghosh Sunita , Pervez Nadeem 
Published: March 2020

e15540 Background: Small cell carcinomas (SCC) of the female genital tract (FGT) are rare and there is no standard treatment strategy for managing these patients (pts). The objectives of this study are to report the clinical experience and management of pts with SCC of the FGT, treated at the Cross Cancer Institute, Edmonton, AB, Canada from 1982 to 2009. Methods: A retrospective chart review of all pts diagnosed with SCC of the FGT between 1982 and 2009 was undertaken. Data was collected on demographics, clinical and pathological characteristics, and patient outcomes. Results: Twenty-seven pts were identified with primary sites as follows: cervix 16 (59%), endometrium 7 (26%), ovary 3 (11%) and vagina 1 (4%). Median age at diagnosis was 53 years. Seventy-eight percent (21/27) had pure SCC; the rest had mixed histology. Seventy percent (19/27) were positive for at least one neuroendocrine marker. Overall, thirty percent (8/27) had limited stage (LS) disease; Seventy percent (19/27) had extensive disease (ES). Treatment of limited stage pts was 3/8 (38%) concurrent chemotherapy with radiation, 3/8 (38%) surgery, 1/8 (12%) chemotherapy alone and 1/8 (12%) radiation alone. For extensive stage pts, 6/19 (31%) treated with surgery with or without adjuvant chemotherapy, 4/19 (21%) concurrent chemotherapy with radiation, 2/19 (11%) palliative chemotherapy and 7/19 (37%) supportive care only. For relapsing pts brain was the site of first distant recurrence in three pts. Median survival for the entire cohort was 7.4 months (25.9 months for limited stage disease and 4.8 months for extensive; p < .0001). Conclusions: SCC of the FGT tract is aggressive with an overall poor prognosis. There is no standard of care for these pts and they are often treated according to local protocols based on data extrapolated from SCC lung cancer. Incidence of brain metastasis as the site of first relapse is relatively lower in FGT SCC, suggesting unclear benefit to prophylactic cranial irradiation.
Pelvic irradiation versus pelvic irradiation with concurrent chemotherapy followed by extrafascial hysterectomy in the treatment of locally advanced cervical cancer in Honduras.
Authors: Henriquez Cooper Hoover Rodyl , Chuang Linus T. , Cardenas Joel , Zelayas Pedro Guillermo 
Published: March 2020

e15556 Background: Because of the lack of brachytherapy in Honduras, patients with locally advanced cervical cancer underwent extrafascial hysterectomy after upfront pelvic irradiation or pelvic irradiation with concurrent chemotherapy. Methods: We compared the effect of pelvic radiotherapy with that of pelvic radiation and concurrent chemotherapy with cisplatin in women with advanced cervical cancer. Between 2008 and 2011, 165 women with advanced cervical cancer confined to the pelvis (stages IB2 through IIIB) received either 70 Gy of radiation to the pelvis alone or with concurrent weekly cisplatin. Patients underwent subsequently extrafascial hysterectomy six weeks after completion of radiation therapy. Results: Of the 165 eligible patients, 90 (54.5%) patients received only pelvic radiation therapy, and 75 (45.5%) patients received pelvic radiation and chemotherapy. Squamous cell carcinoma was identified in 135 (82%) cases and adenocarcinoma in 30 (18%) cases. On the final hysterectomy specimen, 69 (77.8%) patients who received pelvic radiation had a complete clinical response with no residual diseases; there were 40 (53.3%) patients who received pelvic radiation and chemotherapy achieved a complete response (p<0.001). In the group of patients that were treated with pelvic radiation and chemotherapy, only 25 out of 75 (33.3%) patients received the required cisplatin on schedule. The complete clinical response rate of the 25 patients who received the complete course of pelvic radiation and chemotherapy was 80%. Conclusions: Treatment of locally advanced cervical cancer in low-resource settings is met with challenges including the lack of brachytherapy, and unpredictable availability of chemotherapy. Only 33% of patients that were treated with the intention of concurrent chemo-radiation were able to receive cisplatin on schedule. This resulted in a significantly lower response in the patients who were treated with pelvic radiation and chemotherapy. In settings where the availability of chemotherapy is not always available, primary pelvic radiation for advanced cervical cancer resulted in a better treatment response.