bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative risk of HTN and major cardiovascular events associated with use of androgen receptor antagonists for nonmetastatic, castration-resistant prostate cancer.
Authors: Jahan Nusrat , Mogollon-Duffo Francis , Rehman Shabnam , Singal Sakshi , Hardwicke Fred L. 
Published: May 2020

e17605 Background: Metastatic, castration-resistant prostate cancer (mCRPC) is a lethal disease, often preceded by nonmetastatic, castration-resistant phase. Recently, three androgen receptor (AR) antagonists — apalutamide, enzalutamide, and darolutamide — have been approved for nonmetastatic, castration-resistant prostate cancer (nmCRPC). AR-antagonists have been associated with increased risk of hypertension (HTN) and major cardiovascular (CV) events. We conducted a systematic review and meta-analysis of the published phase 3 randomized controlled trials (RCTs) to determine the relative risk of HTN and major CV events associated with use of AR-antagonists for nmCRPC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts from inception until November 2019. Published phase 3 RCTs using AR-antagonists in the study arm for nmCRPC and reporting the number of events of HTN and major CV events were included in the analyses. We used Mantel-Haenszel (MH) method and random effects model to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value and Cochran’s Q-test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) randomizing 2687 patients in the AR-antagonist arms and 1417 patients in the control arms were included in the final analysis for HTN. SPARTAN did not include data for major CV events; hence, other two studies comprising 2903 patients were analyzed for major CV events. Major CV events included myocardial infraction/coronary artery disease, ischemic/hemorrhagic cerebrovascular events, and heart failure. AR-antagonists used in the study arms were — ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy. Randomization was 2:1 in all studies. The pooled RR of any-grade HTN is 1.5 (95% CI: 1.03 – 2.18, p = 0.03, I2 = 70%); and, the pooled RR of grade ≥3 HTN is 1.39 (95% CI: 1.03 – 1.88, p = 0.03, I2 = 13%). The pooled RR of any-grade major CV events is 1.49 (95% CI: 1.05 – 2.13, p = 0.03, I2 = 0%); and, the pooled RR of grade ≥3 major CV events is 1.80 (95% CI: 1.11 – 2.92, p = 0.02, I2 = 0%). Conclusions: Our meta-analysis demonstrated use of AR-antagonists for nmCRPC is associated with increased risk of HTN and major CV events. A careful selection of patients and aggressive management of the CV risk factors are crucial to enhance safety and proper utilization of these promising drugs.
Safety and tolerance of androgen receptor antagonists in nonmetastatic, castration-resistant prostate cancer.
Authors: Wongsaengsak Sariya , Jahan Nusrat , Hardwicke Fred L. 
Published: May 2020

e17607 Background: Metastatic castration resistant prostate cancer (mCRPC) is a fatal disease. Nonmetastatic, castration-resistant prostate cancer (nmCRPC) often predates mCRPC. Recently, three androgen receptor (AR) antagonists i.e. apalutamide, enzalutamide, and darolutamide have been approved for nmCRPC. Nonetheless, any new therapeutic approach poses new safety concerns. We conducted a systematic review and meta-analysis of the published phase 3 randomized controlled trials (RCTs) to determine the safety and tolerance of AR-antagonists in nmCRPC patients. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until November 2019. Published phase 3 RCTs using AR-antagonists in the study arm for nmCRPC were included in the analyses. We used Mantel-Haenszel (MH) method and random effects model to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value and Cochran’s Q-test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) comprising 2687 patients in the AR-antagonist arm and 1417 patients in the control arm were included in the final analysis. AR-antagonists used in the study arms were following— ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy (ADT). Randomization was 2:1 in all studies. No publication bias was appreciated all three studies. The pooled RR of any-grade adverse events (AEs) is 1.08 (95% CI: 1.02 – 1.14, p = 0.01, I2 = 79%) which was statistically significant. The pooled RR of grade ≥ 3 AEs was also significant at 1.32 (95% CI: 1.19 – 1.46, p < 0.00001, I2 = 0%). The pooled RR of grade 5 event is 2.67 (95% CI: 0.79 – 9.02, p = 0.11, I2 = 70%) which was not statistically significant. The pooled RR for discontinuation of treatment regimen was also statistically significant at 1.31 (95% CI: 1.00 – 1.72, p = 0.05, I2 = 35%). Conclusions: In nmCRPC patients, AR-antagonists in combination with ADT is associated with a mild increase risk of any-grade AEs, grade ≥3 AEs, and treatment discontinuation secondary AEs. However, AR-antagonists were not associated with a significantly increased risk of death due to AEs. Careful clinical vigilance and timely intervention with appropriate supportive care are critical to prevent AEs related morbidities and prevent treatment discontinuation.
Sequential or concomitant radiotherapy treatment for patients with localized prostate cancer.
Authors: Venkitaraman Ramachandran , Harihar Lakshmi , Sabar Muhammad , Scrase Christopher D. 
Published: May 2020

e17610 Background: External Beam radiotherapy is a standard treatment for patients with intermediate risk localised prostate cancer. Commonly the radiotherapy plan is delivered in two phases with adequate margins, the first phase to the prostate and seminal vesicles and the second phase to the prostate alone. The two phases can be delivered by intensity modulated radiotherapy as a sequential or concomitant treatment. We compared the toxicities and clinical outcomes of patients who received radiotherapy either as sequential or as concomitant treatment. Methods: Two hundred and twenty five consecutive patients with intermediate risk prostate cancer were included in the study. The patients who had sequential treatment received 60 Gy in 30 fractions to the prostate and seminal vesicles,, while patients who had concomitant treatment received 60 Gy in 37 fractions. All patients received 74 Gy in 37 fractions to the prostate. The Genitourinary (GU) and Gastrointestinal (GI) toxicity data and outcomes in terms of biochemical progression free survival were compared. Results: One hundred eighty patients received sequential radiotherapy, while forty five patients received concomitant radiotherapy. Acute GI toxicity was significantly less in the patients who received concomitant radiotherapy, during weeks four(p = 0.03), six(p = 0.03) and eight(p = 0.06) of treatment, compared to patients who receive sequential radiotherapy. Acute GU toxicities were similar in both groups of patients during treatment. Late GU and GI toxicity at 1 year and 2 years were similar. 3 year biochemical Progression free survival was 90 % for patients who received either sequential compared to 75 % for patients who received concomitant radiotherapy, though not statistically significant (log rank p value = 0.173). Conclusions: Concomitant radiotherapy to prostate and seminal vesicles resulted in lower acute gastrointestinal toxicity compared to sequential radiotherapy to the prostate and seminal vesicles as two phases. The genitourinary and late toxicities were similar. Biochemical progression free survival for patients who received concomitant radiotherapy treatment, could however be inferior to sequential treatment, probably due to the lower dose per fraction to the seminal vesicles and margins.
Dendritic cell vaccine as an alternative to opioid analgesia in patients with advanced cervical cancer.
Authors: Menshenina Anna P. , Kit Oleg I. , Frantsiyants Elena M. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Tumanyan Sergey V. , Dzhenkova Elena A. , Chalabova Tatiana G. , Selezneva Olga G. , Cherkasova Anna A. 
Published: May 2020

e18022 Background: Locally advanced and progressive cervical cancer is always accompanied by the pain syndrome. The common analgesics include non-steroidal anti-inflammatory drugs and opioids. The purpose of the study was to assess allogeneic dendritic cell vaccine (DCV) as an alternative analgesic in patients with advanced cervical cancer. Methods: The pain syndrome dynamics was assessed in 20 patients with advanced T3-4N1M0-1 cervical cancer receiving subcutaneous paravertebral injections of allogeneic DCV in a total alternating dose of 5-10 million cells every 2 weeks. Patients received DCV for one year, with a total of 24 vaccine therapy sessions and a total dosage of 180 million dendritic cells. The pain intensity was assessed on a verbal rating scale: 0 – no pain; 1 – mild pain; 2 – moderate pain; 3 – severe pain; 4 – extremely intense pain. Results: Prior to the therapy, 15 patients (75%) had severe pain; 2 (10%) - moderate pain; 3 (15%) - extremely intense pain. After 4-6 DCV injections, the pain intensity decreased, patients refused opioid analgesics. After 10-12 DCV sessions, 19 (95%) (p < 0.05) women had no pain at all, patients denied additional pain relief with non-opioid analgesics. Unrelieved pain was registered only in one cervical cancer patient. Conclusions: DCV injections in patients with advanced cervical cancer provide pain relief thereby improving their quality of life.
Hormonal rehabilitation in patients with endothelial and cervical cancers.
Authors: Chernikova Natalia V. , Moiseenko Tatiana I. , Shikhlyarova Alla I. , Verenikina Ekaterina V. , Poryvaev Yuriy A. , Myagkova Tatiana Yu. , Kruze Polina A. , Zhenilo Oksana E. , Cherkasova Anna A. , Chalabova Tatiana G. , Kit Oleg I. 
Published: May 2020

e18025 Background: Young patients with early stages of gynecological cancers often go through surgical menopause which worsens the quality of life affecting social, sexual, psycho-emotional, cognitive spheres, and causes somatic diseases rare in a young age. The purpose of the study was to evaluate the clinical effectiveness of medical and hormone replacement therapy (HRT) in patients with endothelial (EC) and cervical cancers (CC) of the reproductive age after surgical treatment. Methods: Clinical data and adaptive reactions were studied in 346 patients with stage Ia-IIa EC and CC aged 20-45 years after combination treatment. Patients were divided into 3 groups: group 1 – 192 patients, estrogen/gestagen HRT; group 2 – 112 patients, treatment with phytoestrogens; group 3 – 42 patients choosing not to have any adjuvant therapy. The Kupperman index was used to evaluate the severity of a post-castration syndrome. Results: In group 1, 158 women (82.3%) showed normal somatic and psychoemotional status and adequate cognitive functions, the Kupperman index ≤20; 34 (17.7%) patients of group 1 needed additional sedation, the Kupperman index = 30; adaptive reactions included reactions of training and adaptation. In group 2, 112 patients (100%) demonstrated moderate hormonal imbalance signs: vegetative and emotional disorders, decreased libido, manifestations of the metabolic syndrome, the Kupperman index = 30-35; adaptive reactions included reactions of training and stress. All patients of group 3 (n = 42) developed metabolic disorders shortly after surgical castration, with social, sexual and psycho-emotional disadaptation, the Kupperman index = 35 (reactions of stress). Conclusions: Combination HRT after surgical castration contributes to full adaptation in the social, sexual, psycho-emotional spheres of life in patients of the reproductive age, restoring the quality of life without affecting the prognosis.
Patient-reported outcomes (PRO) in the GARNET trial in patients (pts) with advanced or recurrent dMMR/MSI-H endometrial cancer (EC) treated with dostarlimab.
Authors: Kristeleit Rebecca Sophie , Mathews Cara Amanda , Redondo Andres , Huang Joice , Eliason Laurie , Im Ellie , Brown Jubilee 
Published: May 2020

e18032 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts (with an ORR of 42.9% and a disease control rate of 58.6%), and a low incidence of symptomatic grade ≥3 treatment-related adverse events (anemia [2·9%], colitis [1·9%], and diarrhea [1·9%]). Here, we report on PRO measures collected from pts with dMMR/microsattelite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used to evaluate quality of life, functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were high at 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. Quality of life and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and quality of life are improved or maintained while receiving treatment. These data, along with with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Clinical trial information: NCT02715284.
Outcomes among women with brain metastases from gynecologic (gyn) malignancies.
Authors: Cagino Kristen , Kahn Ryan , Chan Susie , Thomas Charlene , Christos Paul J. , Pannullo Susan , Ashmalla Hani , Holcomb Kevin , Frey Melissa Kristen , Chapman-Davis Eloise 
Published: May 2020

e18034 Background: Brain metastasis secondary to gyn malignancy is rare and associated with poor prognosis, with limited available data and no definitive management guidelines. We aimed to identify factors and treatments associated with improved overall survival (OS). Methods: Patients were identified retrospectively with brain metastases from gyn malignancies between 2004-2019. Descriptive statistics were used to describe the cohort of patients using N (%) and median [IQR] for categorical and continuous variables, respectively. Univariate cox proportional hazards regression was performed to evaluate the effect of different prognostic factors on OS. Results: 32 patients presented with brain metastasis from gyn primaries (ovarian/primary peritoneal n = 14, cervical n = 7, uterine n = 11). Median age of initial cancer diagnosis was 62 (54-59). At initial diagnosis 83% of patients were Stage III/IV and underwent surgical management (56%), chemotherapy (100%), or pelvic radiation (31%). The median time from cancer diagnosis to brain metastasis was 18mos. 66% presented with multiple; 34% with isolated brain metastases. The most common presenting symptoms were extremity weakness/numbness (78%), seizures (34%), and headaches (28%). Surgical resection was most often combined with stereotactic radiosurgery (SRS) and/or whole brain radiation therapy (WBRT) (Table 1). Median survival from date of brain metastases was longer in patients treated by SRS alone compared to WBRT alone (95 vs 11 mos). Treatment with SRS + Surgery compared to SRS or WBRT alone revealed a trend toward improved OS (p = .06; p = .07). Increased time from initial cancer diagnosis to brain metastasis was associated with improved OS, with one-month increase in time associated with a 7% reduction in risk of death (p = 0.01). Initial cancer treatment, Stage, histology, and number of brain lesions did not affect OS. Conclusions: Patients with brain metastasis secondary to gyn malignancies with the longest OS had the greatest lag time between initial cancer diagnosis and brain metastasis diagnosis. Treatment with multimodal therapy with radiation and surgical resection was associated with the longest OS. [Table: see text]
Real-world treatment patterns of maintenance therapy in platinum-sensitive recurrent epithelial ovarian cancer: Are some patients missing out?
Authors: Moss Haley , Secord Angeles Alvarez , Perhanidis Jessica , Hawkes Carol 
Published: May 2020

e18042 Background: The clinical utility of maintenance therapy (MT) for patients with platinum-sensitive recurrent ovarian cancer (PSROC) has been validated in several clinical trials. We assessed real world treatment patterns using a US nationwide electronic health record database. Methods: A retrospective study of patients with PSROC between March 2017 and July 2019 was conducted using the Flatiron Health database. This longitudinal, demographically and geographically diverse de-identified database covers > 2.2 million oncology patients in > 280 cancer clinics. Patients were excluded if second or third line (2L or 3L) platinum-based chemotherapy (PBT) regimens included less than four or more than eight cycles of platinum. Information regarding somatic or germline BRCA mutations and homologous recombination deficiency (HRD) were obtained. Results: 2292 patients with PSROC were identified (had 2L or 3L treatment); 1214 of these received PBT at recurrence; 610 completed the PBT for recurrence on or after March 2017; 351 received 4–8 cycles of PBT; 225 patients had ≥2 months of active surveillance or were receiving MT of PARPi or bevacizumab (B) and were included in this analysis. 183 patients (80%) had BRCA testing and 14 patients (6%) had HRD testing. 46 (20%) had a germline or somatic BRCA mutations (t BRCA), 134 (59%) had a wildtype wt BRCA gene, and 48 (21%) were unknown. Of patients with tBRCA, 63% received a PARP inhibitor (PARPi), 17% received B, 20% received active surveillance. Of patients with wt BRCA, 40% received a PARPi, 24% received B, and 37% received active surveillance. Olaparib was the most commonly used PARPi among tBRCA patients (26%), while niraparib was most commonly used among wt BRCA patients (21%). MT was more common in younger patients, those with a better performance status and with a BRCA mutation. MT use trend increased by 21% during the study period. As PARPi use increased, the use of active surveillance as a post-platinum regimen decreased during the later time periods (Table). Conclusions: In this real world population, the majority of patients with PSROC are receiving maintenance therapy. While genetic testing is improving, universal testing of all patients with ovarian cancer remains the goal. The results provide insight into the shifting treatment patterns for patients with ovarian cancer. [Table: see text]
CRS + HIPEC in stage IIIc epithelial ovarian cancer and comparison of oncological outcome only with CRS and IV chemotherapy and CRS + IP chemotherapy.
Authors: Somashekhar S.P. , C. Rohit Kumar , Rajgopal Ashwin K. , Yethadka Ramya , Zaveri Shabber , Ahuja Vijay , Rauthan Amit , Patil Poonam 
Published: May 2020

e18054 Background: Our study aims to describe role of CRS & HIPEC in stage IIIC epithelial ovarian malignancy & compare the oncological outcome (DFS & OS) of extensive CRS+ HIPEC in comparison with CRS & IV chemotherapy & CRS + IP chemotherapy. Methods: Patients diagnosed of stage IIIc EOC underwent extensive CRS + HIPEC. All data prospectively entered in the HIPEC registry was analysed. Outcome of CRS & IV group (n = 50), CRS + IP group (n = 60) operated around same period was compared with the CRS & HIPEC group. Results: Out of 135 patients, upfront, interval and secondary cytoreduction plus HIPEC was done in 29.6%, 44.4% & 25.9% & mean PCI was 14.1, 9.6 & 13.0 respectively. Multi-visceral resection, diaphragmatic resection & bowel resection was required in 12.7%, 50% & 41.8% respectively. Overall G3- G5 morbidity was seen in 25.4% with major being electrolyte imbalance 16.3%, hematological 12.7% & surgical 11.8%. Mean ICU & hospital stay 1.5 & 11 days respectively. Overall 30 day mortality was 4.5%. With a median follow up of 42 months DFS was 30, 33 & 16 months and OS was 70%, 67% & 51% at 4 year for upfront, interval and the recurrent settings respectively. Detailed description presented in Table. Most of the recurrences in CRS & IV group were in peritoneum whereas the other two groups had lesser peritoneal & systemic recurrence. Conclusions: Optimal cytoreduction & some form of IP therapy is needed to improve outcomes. CRS+ HIPEC is feasible in all groups of ovarian cancer with acceptable morbidity & mortality. However the role of single HIPEC in comparison to 6 cycles of IP chemotherapy needs to be evaluated with a well-designed multi-institutional randomised study. [Table: see text]
Sex cord stromal and germ cell ovarian cancer: Is there a racial disparity?
Authors: Reyes Fatima , Guerra Rosa , Liao Cheng-I , Argueta Chris , Mann Amandeep Kaur , Abel Mary Kathryn , Kapp Daniel Stuart , Chan John K. 
Published: May 2020

e18056 Background: We proposed to determine the incidence and presentation of sex cord stromal and germ cell ovarian cancers in various racial groups. Methods: Data was obtained from the United States Cancer Statistics (USCS) and National Cancer Database (NCDB) databases between 2004 and 2016. Chi-squared tests were used for statistical analyses. Results: Of 8,917 women, 48.2% were diagnosed with sex cord stromal ovarian cancer, and 52.5% had germ cell ovarian cancer. White, Black, and Asian individuals comprised 72.5%, 19.8%, and 4.16% of the population, respectively. Of the sex cord stromal tumors, 84.1% were granulosa cell, 7.9% sertoli leydig, 1.8% steroid cell, and 6.2% "other" tumors. Of the germ cell tumors, 23.3% were immature teratoma, 19.6% dysgerminoma, 10.3% yolk sac, 8.3% mixed germ cell tumor, 0.1% embryonal carcinoma, and 38.3% "other" germ cell tumor histologies. Using the UCSC database, the age-adjusted incidence of sex cord stromal was 0.50 per 100,000 for Blacks compared to 0.23 for Whites and 0.14 for Asians. The incidence for germ cell tumors was 0.40 per 100,000 in Whites, 0.46 in Blacks, and 0.44 in Asians. Using NCDB data, the proportion of sex cord stromal tumor was 5.6% in Blacks compared to 1.5% in Whites and 1.55% in Asians, and the most common histology of sex cord stromal tumors was granulosa cell tumors in every racial group. The proportion of germ cell tumors was also higher in Blacks at 4.4% compared to 2.0% in Whites and 3.9% in Asians. Of germ cell tumors, the most common histology was dysgerminoma for Whites at 22.3% and immature teratoma in Blacks and Asians at 28.0% and 26.9%, respectively. Conclusions: Our data suggest that Black women are more likely to be diagnosed with sex cord stromal tumors compared to White and Asian women. Black and Asian women also had more germ cell cancer than White women.