bluuebunny/crossref_metadata_2025_split huggingface dataset:
How much is reasonable to expect about overall survival (OS) benefit when designing studies with new drugs for patients affected by castration resistant prostate cancer (CRPC)? Meta-analysis of 23 randomized clinical trials (RCT) including 17,640 patients.
Authors: Massari Francesco , Maines Francesca , Pilotto Sara , Porta Camillo , Carlini Paolo , Modena Alessandra , Ciccarese Chiara , Sperduti Isabella , Giannarelli Diana , Tortora Giampaolo , Bria Emilio 
Published: March 2020

e16053 Background: Treatment decision making in patients affected by CRPC is difficult because the numerous available therapeutic opportunities can significantly affect OS. To demonstrate that comparing results in absence of head-to-head studies may lead to biased survival estimations, a literature-based meta-analysis was conducted. Methods: Hazard Ratios (HR) with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from phase III trials. Sensitivity analyses were performed according to: 1) Treatment Strategy (TS, Chemotherapy versus Hormonal versus Immunotherapy versus Other), 2) Comparison (Chemotherapy versus Placebo versus Other), and 3) Disease setting with regard to treatment with Docetaxel (DOC),. Testing for heterogeneity was performed as well. Results: A significant heterogeneity for the 3 sensitivity analyses was found (p<0.0001). The cumulative HR in favor of (any) experimental arm was 0.91 (95% CI 0.84-0.99, p=0.028). We found a significant interaction according to the chosen TS (p<0.0001), in fact a significant difference in OS was more likely to be detected in RCT evaluating hormonal drugs (HR 0.76, 95% CI 0.64-0.92, p=0.005) versus studies testing immunotherapy (HR 1.16, 95% CI 0.86-1.56, p=0.31). With regard to Comparison, a significant interaction (p<0.0001) was found in favor of RCT having placebo as control (HR 0.86, 95% CI 0.76-0.97, p=0.015), versus studies evaluating chemotherapy (HR 1.00, 95% CI 0.84, 1.19, p=0.99). A significant interaction according to DOC-treatment was also detected (p<0.0001), being the Post-DOC the Setting where a significant OS benefit was more likely to be determined (HR 0.77, 95% CI 0.66-0.90, p=0.001). Conclusions: The cross-trials interpretation in absence of formal direct comparisons may drive biased conclusions with regard to OS estimation. When designing trials to evaluate drugs (or strategies) in CRPC, the expected OS benefit must take into account the comparator, the treatment strategy and the (eventual) pre-treatment with DOC.
Negative association of smoking with PSA and PSA velocity.
Authors: Algotar Amit Mohan , Sokoloff Mitchell , Hsu Chiu-Hsieh , Singh Parminder , Stratton Steven Paul 
Published: March 2020

e16060 Background: Smoking and obesity have been implicated in the pathogenesis of various chronic diseases and carcinogenic processes. However, their role in prostate cancer (PCa) & their association with important biomarkers such as prostate specific antigen (PSA) & PSA velocity (rate of PSA change over time) remains unresolved. This study investigates the association of these risk factors with PSA & PSA velocity (PSAV) in men at high risk for PCa. Methods: Data were obtained from 699 men participating in a Phase 3 clinical trial aimed at investigating the effect of selenium supplementation on incidence of PCa. During the course of this trial 73 men were diagnosed with PCa. Multiple linear regressions were used to investigate the association with PSA and mixed effects models were used to investigate the association with PSAV. Results: As compared to non-smokers, smokers demonstrated statistically significant negative association with PSA (8.0 & 6.7ng/ml, p=0.02). This association was more pronounced in men diagnosed with PCa (14.7 & 9.9ng/ml) as compared to those not diagnosed with PCa (4.5 & 3.6ng/ml). As compared to non-obese subjects, obese subjects did not demonstrate a statistically significant association with PSA (6.8 & 7.1ng/ml, p= 0.64) nor do these results change after stratifying the analysis by PCa status. Smoking was associated with statistically significant lower PSAV (p=0.008) whereas obesity was not (p=0.42). Using the standard PSA level of 4ng/ml as a cut off for conducting prostate biopsy, 14.6% of smokers in this study would not have been prescribed a prostate biopsy and thus misclassified as being negative for PCa. Conclusions: The negative association of smoking with PSA and PSA velocity could potentially be due to its negative effect on testosterone. Hence, increased vigilance may be warranted among smokers with borderline PSA to prevent the risk of delayed diagnosis and metastasis thus reducing morbidity and mortality associated with PCa.
Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) refractory to docetaxel (D).
Authors: Peer Avivit , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Boursi Ben , Leibowitz-Amit Raya , Berger Raanan , Neumann Avivit , Kovel Svetlana , Sella Avishay , Pili Roberto , Hammers Hans J. , Sinibaldi Victoria J. , Carducci Michael Anthony , Eisenberger Mario A. , Keizman Daniel 
Published: March 2020

e16068 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to D. It is a potent and selective CYP 17 inhibitor, that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. Aims: To compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.
Comparison of the pharmacokinetics (PK) of galeterone novel oral formulations.
Authors: Kramer William G. , Vince Bradley , McGarry Carolyn 
Published: March 2020

e16075 Background: Galeterone (gal) is an orally available steroid analog for the treatment of castration resistant prostate cancer (CRPC). A significant food effect, similar to abiraterone, was found when gal, as powder in capsule (PIC), was dosed in a phase I CRPC trial and confirmed in a PK study in human volunteers.The objective of this study was to assess single-dose PK of gal after reformulation and to evaluate effect of food. Methods: In this single-center open-label study, 24 male subjects were assigned to receive once daily doses of between 100 and 3400 mg in either a 3-treatment, 3-period or 4-treatment, 4-period dose scheme. Treatment periods were separated by 7-day washout intervals. Plasma concentrations were measured over 72 hours to assess PK. Two novel tablet formulations were administered in 100 mg doses under fasted and/or fed condition compared to 2600 mg-PIC administered under fed conditions. Escalating doses of PIC (975 to 2600 mg) and tablet (850 to 3400 mg) formulations were evaluated to assess linearity. Results: Gal was well tolerated. Food effect has been negated with the tablet. Exposure from 1700 mg galeterone tablet (fed or fasted) is comparable to a 2,600 mg dose of PIC (fed) (Table). For tablet, AUC(inf) increased in a dose-related and dose-proportional manner from 6,689 ± 2,602 hxng/mL (850 mg) to 20131 ± 9,930 hxng/mL (2,550 mg). Conclusions: The tablet formulation negates the food effect previously observed. Gal may be dosed either fed or fasted with no difference in absorption, which reduces intra-patient variability in exposure. Tablet has more consistent bioavailability and a linear increase in AUC between escalating doses. [Table: see text]
Quality of life (QoL) of patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel.
Authors: Winquist Eric , Sridhar Srikala S. , Hubay Stacey , Assi Hazem , Berry Scott R. , Alloul Karine , Levesque Eric , Aucoin Nathalie , Czaykowski Piotr , Saad Fred 
Published: March 2020

e16088 Background: The effects of cabazitaxel on QoL, pain response and preference/utility data have not been well studied in men with CRPC treated post-docetaxel. As part of a single-arm multicenter Sanofi-funded Early Access Program (EAP) for cabazitaxel, QoL data were collected on Canadian patients. Methods: Between May 2011 and February 2012, 61 patients (pts) were enrolled at 9 centers. QoL was assessed at the start of each cycle using the FACT-P and its subscales, and the EQ 5D-3L. EQ 5D-3L health state index (HIS) data were converted into utility values (Canadian tariff, Bansback 2011). Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. Results: QoL data were evaluable in 55 pts. Baseline pt characteristics were: median age 65 years (range, 42-79), 92.7% of pts were ECOG PS 0 or 1, 87% had bone metastases, and 56% (31/55) received at least 6 cycles of cabazitaxel. Statistically significant changes from baseline in mean QoL scores were observed on FACT-P total score at cycle 2, and prostate cancer specific subscale (PCS) at cycles 1 to 4. As a measure of QoL response, increases were observed and maintained for > 2 consecutive cycles in 9% (>16 points) and 25% (≥10) of pts for FACT-P total score. Improvements to the level of Minimal Important Differences (MID) (Cella 2009) maintained for > 2 consecutive cycles were observed in 36% of pts for FACT-P total score (MID=6), 49% for PCS subscale (MID=2), and 26% for PCS-Pain subscale (MID=2), respectively. The percentage of pts reporting "no problem" in the EQ-5D pain/discomfort domain were above baseline levels at every cycle and improved from baseline to end of treatment from 19% to 29% (p < 0.05). Other EQ-5D dimensions (anxiety/depression, mobility, self-care and usual activities) remained stable over the course of treatment. Improvement from baseline in utility value (HIS) was observed at cycle 4 with a utility value of 0.769 (vs 0.713 at baseline). PPI scores improved despite stable analgesic use and were significantly different from baseline at cycles 2, 4 and 9. Conclusions: Data from this EAP suggest improvements in QoL, pain and prostate cancer specific symptoms with second-line cabazitaxel treatment. Clinical trial information: NCT01254279.
Cost of palliative external beam radiotherapy (EBRT) utilization for bone metastases secondary to prostate cancer (PC).
Authors: Nickman Nancy A. , Ye Xiangyang , Gaffney David K , Barney Reed B. , Biskupiak Joseph E. , Okano Gary J. , Lee Vinson C. , Arellano Jorge 
Published: March 2020

e16091 Background: Evaluations of palliative EBRT costs for patients with bone metastases are limited. The objective of this study was to summarize documentation of usual care patterns and episode costs of EBRT to bone in deceased men with metastatic PC treated in a United States specialty cancer hospital. Methods: An Electronic Health Record (EHR)-based retrospective review was used to identify deceased PC (ICD-9 185.xx) patients ≥18 years of age with bone metastases (ICD-9 198.5) treated between 1995 and 2012 with EBRT for metastasis and pain management. Variables of interest encompassed patient-specific demographic and clinical characteristics, including length and number of EBRT treatments and total cost of EBRT usage (standardized to 2011$US).Common Procedural Terminology (CPT) codes related to EBRT and hospital assigned visit numbers were used in an algorithm to identify EBRT episodes of care (defined as all billed professional and technical EBRT services provided between initial and final evaluation by radiation oncologist). Bootstrapping (percentile method) was used to approximate the 95% confidence interval for final EBRT cost estimates. Results: A cohort of 176 men were identified; 19 (10.8%) had metastases in >1 site, and an average (±SD) Charlson Comorbidity Index of 6.4 ± 3.9 at metastasis diagnosis (excluding cancer). An average of 5.1 ± 4.6 years elapsed between PC and bone metastasis diagnoses. Prior to bone metastasis diagnosis, patient-reported symptoms included bone pain (54%). All men received at least 1 episode of EBRT, and 89 (50.6%) received >1 episode (range 1-6, median = 2). The length of first episode of EBRT ranged from 1 - 44 calendar days (average ± SD, 13.4 ± 8.4), with an average cost totaling $7,084 ± $4,028. Approximately 70% of costs were attributable to hospital (technical) charges and 30% to physician (professional) charges. Bootstrapping resulted in a 95% confidence interval of total cost between $6,641 and $7,527. Conclusions: Results suggest thatpalliative EBRT may constitute a significant burden in time and healthcare system costs.
Zoledronic acid for hormone-naive prostate cancer with bone metastasis.
Authors: Nozawa Masahiro , Hara Isao , Nagao Kazuhiro , Matsuyama Hideyasu , Uemura Hirotsugu 
Published: March 2020

e16092 Background: The potency of zoledronic acid for hormone-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefit of administering zoledronic acid concomitant with androgen-deprivation therapy in treatment-naïve prostate cancer patients with bone metastases, in which the primary endpoint was skeleton-related event (SRE)-free survival at 24 months after treatment. Methods: Treatment-naïve male patients with histologically confirmed adenocarcinoma of the prostate and radiologic evidence of bone metastasis were eligible. Treatment consisted of bicalutamide 80 mg administered orally on Day 1 and every day, goserelin acetate 10.8 mg administered subcutaneously on Day 8 and every 12 weeks, and zoledronic acid 4 mg administered intravenously on Day 8 and every four weeks. Results: Between July 2008 and April 2010, a total of 53 patients were enrolled and 52 evaluable. Median age was 72 years (range, 55 - 86). Median primary PSA was 249.4 ng/ml (range, 2.19 –19201). Median follow-up period was 33.3 months. The SRE-free survival rate at 24 months after treatment was 82.7 %. Median time to PSA progression was 25.9 months (95% confidential interval, 17.97-24.43). The score of the extent of bone diseases was stable or decreased in 73 % of the patients at 24 months after treatment. The grade-3 osteonecrosis of the jaw was reported in three patients (5.8 %). Conclusions: Our results suggest the potency of the early introduction of zoledronic acid for prostate cancer patients with bone metastases. Future studies are certainly required to ascertain the most appropriate timing of the commencement of zoledronic acid for patients with bone-metastatic prostate cancer. Clinical trial information: UMIN000007548.
Relation between the disease-free period and body mass index in prostate cancer patients with high-risk prognosis.
Authors: Richardet Eduardo Arnoldo , Laura Perelli , Molina Matias , Brombin Romina , Richardet Martin 
Published: March 2020

e16100 Background: To determine, according to BMI, whether overweight and obesity in patients with high risk prognosis in prostate cancer is associated to a shorter disease-free period. Methods: We conducted a retrospective and descriptive study of the population from Instituto Oncológico de Córdoba, in patients with prostate cancer. Prostatectomized, with a high risk according to the College of American Phathologists Consensus Statement served between the year 2000 and 2010, we observed that 52 patients met these characteristics with a average age of 70.16 years, range of 48-87 and those were divided into two groups according to their BMI in equal or greater value than 26 and in another group those in equal or smaller than 25. Results: From the 52 patients, 27 (51.92%) had a BMI equal or greater than 26, those who experienced relapse, in average, at 25.33 months; while 25 patients (48,08%) had a BMI equal or smaller than 25, with an average relapse time of 28.35 months, presenting a p=0.11 Conclusions: We observed that patients with overweight and obesity had a tendency towards relapse before patients with a normal BMI. Further sample size would be needed to establish statistically significant differences.
Liver metastases in carcinoma of the prostate as an indicator of aggressive subtype refractory to hormonal therapy and duration of response to docetaxel monotherapy: A single institution experience.
Authors: Singh Arsh , Kafeel Muhammad I. , Shakil Shams A. , Gulmi Frederick , Mooppan Unni , Wang Jen C. 
Published: March 2020

e16101 Background: Prostate cancer exhibits distinct pattern of metastasis with bone being the most common site of involvement. Liver is an uncommon site of metastasis and is associated with poor prognosis. Very few data is available on treatment with hormone including LHRH agonist (LA) and abiraterone (Ab) and chemotherapy. We retrospectively reviewed data of patients with liver metastasis with the primary objective of determining their clinical characteristics and treatment outcome from a single institution experience. Methods: Data of 5 patients with prostate cancer who developed liver metastases during the course of their disease was collected between 2007 and 2013. Four out of five patients had histological confirmation of prostatic origin adenocarcinoma while one had radiological confirmation. All patients except one had received prior LA and all were chemotherapy naïve prior to development of liver metastases. Objective biochemical response was defined as >50% decrease in PSA value following therapy. Results: Gleason score was >8 in 4/5 patients and unknown in one. Three out of five patients who progressed on LA received docetaxel, and despite achieving a more than 50% objective PSA response in all patients, it was of short duration, the mean duration of response was only 6 months. Two patients received Ab, after chemotherapy with docetaxel ,did not show any response and another two patients received LA therapy also failed ( one patient who presented with lung metastases developed liver metastases in <6 months; one patient who presented with liver metastases expired in <3 months despite LA therapy). Thus, four of five patients in this small series did not respond to hormone therapy. Conclusions: From this small series of study, it suggests that liver metastases in carcinoma of prostate represent an aggressive subset that does not respond to hormonal therapy including the LHRH agonist and abiraterone. Although they responded to docetaxel chemotherapy, the responses were of short duration. An alternative regimen should be explored for this particular subset of patients.
Fecal and urinary incontinence impairing social functioning and quality of life among survivors of gynecologic cancers.
Authors: Pushpalatha Kameshwarachari , Sharma Dayanand , Kumar Sunesh , Julka Pramod Kumar 
Published: March 2020

e16511 Background: Fecal and urinary incontinence are late side effects of pelvic radiotherapy and are termed as most bothersome causes for distress and detachment among survivors of gynecological cancers. The present study was conducted to find out the impact of fecal and urinary incontinence on quality of life with regard to psychological, social and sexual functions. Methods: A cross-sectional study was conducted between June 2010 - June 2011 on cohort of 100 advanced cervical cancer patients treated with pelvic radiation of 50.4 Gy in 28 fractions over 5.5 weeks and concurrent cisplatin, followed by intracavitary boost of 15 Gy. By using a questionnaire addressing social, psychological, sexual concerns, data was collected with respect to loss of interest in social parties, travelling, domestic performance, sexual life, personality changes. Results: Fecal incontinence was seen in 17% and urinary incontinence in 28% which affected quality of life (58%). The impact of these symptoms reflected on refraining from participation in social gatherings (20%) and travelling (18%), decreased performance in domestic activities (32%), fear of losing support of spouse and children especially owing to malodour of urine and feces (35%), lack of interest in pursuing sexual intimacy (25%), apathy (18%), fear of disease recurrence (35%), fear of death (42%). Conclusions: Although psychosocial and sexual issues are less openly addressed in the clinics, structured patient-doctor discussion to envisage and demystify longstanding misconceptions concerning sexual function, psychological education by psychotherapists coupled with social support by system-wide dissemination of awareness in the form of pamphlets, books, videos, websites and other visual aids to patients can maintain the quality of life in such patients. Satisfaction regarding discussions on these issues may also vary depending on oncologic specialty clinic, age of the patient and the gender of her oncologist. Timely intervention to minimize these problems would result in significant increase in the followup rates and prolong the survival of the cancer patients.