bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcome (CO) and predictive factors (PRE) evaluation of young (≤ 60 years) castration-resistant prostate cancer (CRPC) patients, treated with docetaxel (DOC): Preliminary results of an Italian multicenter retrospective study (CYCLOP study).
Authors: Caffo Orazio , Ortega Cinzia , Di Lorenzo Giuseppe , La Russa Francesca , Burgio Salvatore Luca , Messina Caterina , Facchini Gaetano , Iacovelli Roberto , Lodde Michele , Morelli Franco , Massari Francesco , Procopio Giuseppe , Zustovich Fable , Lo Re Giovanni , Pegoraro Cristina , Gamucci Teresa , Pappagallo Giovanni L. , Veccia Antonello , Maines Francesca , Galligioni Enzo
Published: March 2020

e16031

Background: CRPC is rare in pts ≤ 60 yrs and clinical outcomes of these pts are not clearly defined despite there is a common feeling of a worse prognosis for them. The present study is aimed to assess CO and PRE in this specific population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all < 60 yrs CRPC pts from participating institutions, treated with DOC. We recorded the pre and post-DOC clinical history, the DOC treatment details and outcomes. We have also assessed the ability of a series of selected 18 clinical factors to predict DOC response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 98 pts from 16 Italian hospitals. The median age was 57 yrs (range 41-60). The median baseline PSA was 84 ng/ml (range 2-2721); 93% of the pts had bone metastases while 49%, 9%, and 13% showed nodal, liver and lung metastases, respectively. All but 8 pts received DOC with a 3-week standard schedule: the median number of received DOC courses was 8 (range 1-14). The main grade 3-4 toxicities were anemia (4 pts), neutropenia (15 pts), febrile neutropenia (1 pt), peripheral neuropathy(1 pt). A PSA reduction > 50% was observed in 61% of the pts while 14% and 7% of the cases showed a partial and complete response, respectively. Having a Gleason score (GS) <8 [p= 0.032], a hemoglobin initial value >12 [p= 0.052], no nodal involvement [p= 0.101], resulted to be independently predictive of a PSA reduction > 50%. The median PFS and OS were 7 mos and 19 mos, while the 1-year PFS and OS rates were 17.3% and 70%, respectively. Conclusions: From these preliminary results, we failed to confirm a worse prognosis for younger CRPC since their survival outcomes are similar to those observed in the pivotal trials. Low GS, absence of nodal involvement and good hemoglobin levels are the only predictive factors.
C-MYC, HER2, and HER3 expression in localized prostate cancer (PC) treated with radical radiotherapy: Modulation by statins use and correlation with time to progression.
Authors: Torrejon Davis Yuri , Suarez Cristina , Maldonado Xavier , Navarro Alejandra , Morales Rafael , Planas Jacques , Valverde Claudia María , Nuñez Isaac , de Torres Ines , Morote Juan , Hernandez-Losa Javier , Carles Joan
Published: March 2020

e16045

Background: There has been growing interest in the activity of statins (St) in PC patients receiving definitive radiation therapy. The oncogene Ras can be inhibited by HMG-CoA reductase inhibitors that in turn are also able to downregulate Myc. The aim of this study was to correlate St use and progression with the c-Myc, HER2 and HER3 expression in PC treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: A total of 85 patients diagnosed with localised PC between 2000 and 2005 were selected for the study. Inmunohistochemical assay on core biopsy of each patient was performed using monoclonal antibodies for c-Myc, HER2 and HER3. The expression was evaluated using a semiquantitative method (Hscore scale: 0 to 300). Clinical and pathological variables were compared between St users and non-users and correlated with expression of c-Myc, HER2 and HER3. St users were defined as patients who had been taking St for at least 2 years before the diagnosis of PC and during follow up. Time to progression (TTP) was analyzed. Results: Mean age was 71 (56-82) years. Median follow-up was 75 months after RT. Twenty-five patients (29.4%) were using St. No statistical differences were found between treatment groups regarding median age, risk category, clinical T stage, Gleason score or median radiation dose. Median Hscore value of c-Myc was 40 (5-210) for St users vs. 72.5 (5-280) for non-users (p = 0.01). Only 8.6% of the cases showed HER2 expression and in those staining was mild intense and focal. Moderate expression of HER3 was observed in 36 cases (41.8%) and no correlation with St users nor with TTP was demonstrated (p=0.8). At the time of analysis, only 13 pts (15.3%) had biochemical relapse (1 low risk, 3 intermediate, and 9 high risk). St use (46.2%) was significantly associated with improved TTP (55 vs. 36.2 months, p = 0.022). Conclusions: Our work implicates a correlation of St use with a significant lower c-Myc expression and improvement in TTP in all groups, regardless the risk. No correlation was reported between HER2 or HER3, TTP and St use.
Influence of concurrent medications on PSA doubling time (PSADT) in patients (pts) with nonmetastatic biochemically relapsed prostate cancer (BRPC M0) after local therapy (tx).
Authors: Mermershtain Wilmosh , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Rouvinov Keren , Pili Roberto , Hammers Hans J. , Sinibaldi Victoria J. , Carducci Michael Anthony , Eisenberger Mario A. , Keizman Daniel
Published: March 2020

e16051

Background: In patients with BRPC(M0) after local tx, the most important prognostic factor is probably the PSADT (high risk < 3, intermediate risk 3–8.9, low risk ≥9.0 months). Pre-clinical and clinical studies in several cancer types have shown that commonly prescribed medications may inhibit tumor growth. The effect of commonly prescribed medications on PSADT in pts with BRPC(M0) is poorly defined. Aims: To study the effect of commonly prescribed medications on PSADT in pts with BRPC (M0) after local tx. Methods: We reviewed the records of 156 BRPC(M0) pts enrolled in 1 prospective (Keizman, CCR 2010) and two retrospective (Keizman, prostate 2012; Mermershtain, EMUC 2011) studies, in 2 centers across 2 countries. The effect of clinicopathologic factors and the use of statins, aspirin, and angiotensin system inhibitors (ASIs; ACE-I and ARBs) on initial PSADT (from the time of first PSA relapse to the initiation of any systemic tx) was analyzed using the Mann-Whitney or Kruskal-Wallis tests and regression analyses. Results: In the whole patient cohort (n=156), median age was 62, prior local tx consisted of radical prostatectomy in128 pts and EBRT in 28, and median PSADT was 6.7 months (mos). Median PSADT in ASIs users (n=48) vs non users (n=108) was 7.85 vs 5.6 mos (p=0.011). In multivariate analysis, the use of ASIs and Gleason score were associated with median PSADT. The use of statins (n=58) or aspirin (n=72), primary tx modality, and time from primary tx to PSA relapse had no significant effect on median PSADT. PSADT risk grouping in ASIs users vs non users was low 48% vs 27%, intermediate 42% vs 49%, and high 10% vs 24% (p=0.02). In multivariate analysis, the use of ASIs, Gleason score, and prior ADT were associated with PSADT risk grouping. The use of statins or aspirin, primary tx modality, and time from primary tx to PSA relapse had no significant effect on PSADT risk grouping. Conclusions: The use of ASIs, Gleason score, and prior ADT may be associated with PSADT (median and risk grouping) of pts with BRPC (M0) after local tx. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials.
International prevalence of nonmetastatic (M0) castration-resistant prostate cancer (CRPC).
Authors: Liede Alexander , Arellano Jorge , Hechmati Guy , Bennett Brian , Wong Steven
Published: March 2020

e16052

Background: CRPC represents a growing public health concern that has not been adequately quantified. In the absence of metastases, CRPC represents a transitional disease state defined by increases in prostate specific antigen (PSA) despite castration levels of androgens during androgen deprivation therapy (ADT). We developed a model to estimate M0 CRPC prevalence in selected countries. Methods: A patient-flow model was developed to estimate 5-year limited duration prevalence of prostate cancer (PC) and M0 PC in each country, each year (2008 to 2028) using age-specific incidence and survival data from population cancer registries from 28 countries in North (US, Canada, Mexico) and South America (Brazil), Europe (18 countries), Asia (5 countries), and Australia. The proportion of men with M0 PC treated with ADT was based on literature reports and survey research with physicians treating PC. PSA relapse rates from published literature were used to estimate CRPC among ADT treated. Results: PC prevalence is driven by size and aging of populations, with notable increases predicted within 15 years in regions other than US, Canada, and EU5 (table). The prevalence model, which utilized country-level data, indicates that M0 CRPC represents a relatively small proportion (2-8%) of the total PC population. Nonetheless, widespread screening and demographic changes dictate that the prevalence of CRPC will increase over the next 15 years, assuming current ADT rates. Conclusions: Incidence trends in PC are dependent on PSA screening, which is projected to lead to an increase in M0 PC and PC prevalence in most regions. The number of men treated with ADT and who ultimately develop CRPC will increase accordingly, as demonstrated in the model. [Table: see text]
Cell-free plasma DNA for the diagnosis and follow-up of prostate cancer patients.
Authors: Wroclawski Marcelo L. , Serpa Ary , Fonseca Fernando L. A. , Neto Oseas Castro Neves , Pompeo Antônio C. L. , Machado Marcos Tobias , Del Giglio Auro
Published: March 2020

e16058

Background: Cell free plasma DNA (CF–pDNA) may have diagnostic and prognostic value in patients with Prostate Cancer (PCa). Methods: We included 133 men with PCa and 33 controls. PCa patients had blood drawn every 3 months for 2 years. CFpDNA was measured by spectrophotometry. Results: CF-pDNA had an area under the curve of 0.824 with a sensitivity of 66.2%, a specificity of 87.9% ,a positive and negative likelihood ratios of 5.46 and 0.39, respectively. There was no statistical significant correlation between CF-pDNA levels at study entry with PSA, Gleason score, stage and biochemical recurrence free survival(BRFS). However, with a mean follow up of 13.5 months, we observed significantly shorter BRFS for patients with at least one value above 140 ng/ mL of CF-pDNA during follow up (p= 0.048). Conclusions: CF-pDNA is a potentially valuable biomarker for PCa diagnosis and may have a prognostic role during follow-up of patients with PCa.
Investigator-initiated pilot study of bicalutamide and raloxifene in hormone-resistant prostate cancer.
Authors: Ho Thai Huu , Northfelt Donald W. , Nateras Rafael Nunez , Bryce Alan H. , Dueck Amylou C. , Castle Erik P.
Published: March 2020

e16065

Background: Estrogens, in addition to androgen may contribute to the progression of prostate cancer.The combination of bicalutamide, a non-steroidal anti-androgen, and raloxifene, a selective estrogen receptor modulator, has a synergistic effect on cell death of prostate cancer cell lines such as DU145 and PC3. We investigated the safety of combined treatment of bicalutamide and raloxifene on quality of life in patients affected by hormone-resistant prostate cancer. Methods: Eligibility requirements included metastatic hormone-resistant prostate cancer, Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the combination of bicalutamide, 50 mg, and raloxifene, 60 mg, daily in 28 day cycles for a maximum of 6 cycles. The primary endpoint was to describe the adverse event profile of combined treatment with bicalutamide and raloxifene. The secondary endpoint was to describe the quality of life of patients receiving the combination. Adverse events were graded by the investigator using the NCI Common Terminology Criteria for Adverse Events version 4.0 and the quality of life was assessed by the patient using aLinear Analog Scale Assessment (scale of 0-100). Serum levels of estradiol and testosterone were monitored during treatment. Results: Eighteen evaluable patients were included in the statistical analysis after an initial run-in safety cohort of six patients. Two patients completed 6 cycles per protocol, the remaining sixteen patients were taken off protocol after disease progression. Patients completed a median of 2 cycles. There were no grade 4 events and grade 3 adverse events consisted of hypertension (5.6%) and back pain (5.6%). Erectile dysfunction (grade 1) was the most common adverse event (77.8%). Patient assessment of quality of life (mental, physical, social, emotional, spiritual) did not reveal any statistically different changes after 2 cycles of treatment. An analysis of testosterone and estradiol levels will be reported. Conclusions: We conclude that combination of bicalutamide and raloxifene is well-tolerated. The combination of androgen and estrogen receptor blockade warrants further study for efficacy in hormone-resistant prostate cancer. Clinical trial information: NCT01050842.
How does stereotactic body radiotherapy compare to standard external beam radiotherapy or low-dose rate brachytherapy for low-risk prostate cancer?
Authors: Sethukavalan Perakaa , Cheung Patrick , Morton Gerard , D'Alimonte Laura , Deabreu Andrea , Mamedov Alexandre , Zhang Liying , Chung Hans T. , Nam Robert , Loblaw D. Andrew
Published: March 2020

e16070

Background: Stereotactic body radiotherapy (SBRT) is an emerging radiotherapy technique that appears to be efficacious, well tolerated and convenient. However, outcomes for patients treated with SBRT are unknown compared to more conventional radiation options for patients with prostate cancer. The purpose of this study is to evaluate and compare late toxicities and biochemical disease-free survival (bDFS) of low risk prostate cancer patients treated SBRT (35Gy/5 fractions), standard external beam radiotherapy (STND; median 76Gy/38 fractions) or low-dose brachytherapy (LDR; iodine-125, 145Gy) at the Odette Cancer Centre. Methods: Consecutive patients with low risk prostate cancer treated with radiation from 2006-2008 were analyzed. Patients treated with SBRT were part of a phase 2 prospective clinical trial; patients treated with STND or LDR had data abstracted from medical charts retrospectively. Patients treated with neoadjuvant androgen deprivation therapy were excluded from biochemical analyses. Univariate (UVA) and multivariate analyses (MVA) of Cox proportional hazard model were conducted to identify significant covariates predicting bDFS. Results: A total of 357 low-risk prostate cancer patients were identified (84 SBRT, 81 STND and 192 LDR). The median follow-up was 57, 62, and 59 months, respectively. At baseline, 85% of patients were T1c, 15% T2a; 100% had GS 6; median PSA 5.9 ng/ml. There were more patients in the STND and LDR cohort who had T2a disease (6%, 21% and 16%, p= 0.013) and the mean PSA was higher in the STND cohort (6.08, 6.69, and 6.02, p=0.017). Patients who received LDR experienced more late hematuria (0%, 1.23% and 11.98%, p<0.0001); otherwise there were no significant differences in late toxicities observed. There were no significant differences in bDFS (97.4% vs 96.9% vs 97.2% at 60 months, p=0.94). There were no covariates identified predicting bDFS on UVA or MVA, including treatment type. Conclusions: SBRT, STND and LDR show equivalent effectiveness and both external beam techniques showed less hematuria than LDR. However, SBRT and LDR are more convenient and less costly than STND. Further prospective studies of SBRT are ongoing.
Skeletal-related events (SRE) and bone-targeted agents for metastatic prostate cancer: Are we changing outcomes?
Authors: Moretto Patricia , Hutton Brian , Kuchuk Iryna , Canil Christina M. , Ng Terry L. , Addison Christina L. , Clemons Mark J.
Published: March 2020

e16074

Background: Bone-targeted agents (BTA) have been extensively studied in patients (pts) with prostate cancer (PC) and bone metastases (BM). Relatively little is known about the impact of BTAs on skeletal morbidity in the non-trial setting. We evaluated the impact BTAs on SRE and survival at a large Canadian cancer centre. Methods: Electronic heath records were reviewed for PC pts referred for further management from January 2008-June 2012. Demographic, clinical, and treatment data including: date of CRPC, occurrence of SRE, and BTA use were collected and analyzed. Results: A total of 141 pt charts were examined and were included in the analysis. Median age was 74 years (IQR 63-82), and 95% were stage IV at time of referral. Consequences of BMs included:101 pts had at least one SRE (72%), 58 (40%) pts had ≥1 SRE and 39% were hospitalised due to an SRE. Median overall survival from diagnosis of BM was 35.4 months (m) (IQR 16.1-65.9). Overall, 74 pts (52%) developed castration resistant PC (CRPC). In the CRPC group, the use of imaging to assess BM was highly variable, ranging from only once (12%) to every 1-2 m (4%), however the mode was every 3-5 m (43%). Sixty one percent (45/74) received a BTA, primarilyzoledronic acid (ZA). Despite having CRPC and BM, 39% never received a BTA, mainly because it was not offered (64%), or due to patient’s refusal (29%). Median time from diagnosis of CRPC to start of BTA was 1 month. Sixty-nine percent of pts had BTA discontinued, mainly due to progression of disease and pts deterioration. Osteonecrosis of the jaw occurred in 4% (2/45). In 39 pts (53%) the first SRE occurred prior to CRPC diagnosis, and 62 pts (84%) had at least 1 SRE after CRPC diagnosis. Forty seven percent (21/45) had a new SRE after starting BTA. Conclusions: BM have significant consequences for pts with PC irrespective of hormone sensitivity. Even for pts with CRPC the use of BTAs is highly variable. This reflects physician’s belief in the efficacy of BTAs, tailored by the expected benefits to each pt according to performance status and extent of disease. Interestingly in the CRPC group 53% have had an SRE prior to CRPC diagnosis. Strategies to optimise the care of pts with BM are clearly warranted.
Utilization and cancer detection by U.S. prostate biopsies (2005-2011).
Authors: Olsson Carl A. , Kapoor Deepak A. , Anderson Ann E. , Mendrinos Savvas E. , Bostwick David G.
Published: March 2020

e16076

Background: To assess the positive biopsy rate and core sampling pattern in patients undergoing prostate biopsy in the US at a national reference laboratory and pathology laboratories integrated into urology group practices and analyze the relationship between positive biopsy rates and number of specimen vials per biopsy (v/b). Methods: For the years 2005-11, we collected pathology data from a national reference laboratory (NRL) including number of urologists and urology practices referring samples, total specimen vials submitted per prostate biopsy, and final diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia or atypical small acinar proliferation. Over the same period, similar data was gathered from urology practices with in-house laboratories performing global pathology services (urology practice labs, UPL) identified by a member survey of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials/biopsy were calculated in aggregate and separately for each site of service. Results: From 2005-11, 437,937 biopsies were submitted in 4,230,129 vials (9.4 v/b); overall positive biopsy rate was 40.3%, identical at both the NRL and UPL (p=0.97). Nationally, the number of specimen vials/biopsy increased sharply from a mean of 8.8 during 2005-8 to 10.3 from 2009-11 (difference 1.5 v/b, p=0.03). For the most recent 3 year period (2009-11), there was no significant difference between the NRL (10.0 v/b) and UPL (10.6 v/b) (p=0.08). Positive biopsy rate correlated strongly (p<0.01) with number of specimen vials/biopsy. Conclusions: The positive prostate biopsy rate of 40.3% is identical across sites of service. Although there was a national trend towards increased specimen vials/biopsy from 2005-11, from 2009-11 there was no significant difference in specimen vials/biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10-12 unique specimen vials has been adopted by urologists across sites of service and can be considered the de facto national standard of care.
Clinical outcome (CO) and predictive factors (PRE) evaluation of a cohort of castration resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate (AA) in a named patient program (NPP): Preliminary results from a retrospective study.
Authors: Veccia Antonello , Fratino Lucia , Basso Umberto , Donini Maddalena , D'Angelo Alessandro , Massari Francesco , Procopio Giuseppe , Gasparro Donatello , Verderame Francesco , Messina Caterina , Zustovich Fable , Iacovelli Roberto , Fraccon Anna Paola , Pappagallo Giovanni L. , Maines Francesca , Caffo Orazio , Galligioni Enzo
Published: March 2020

e16078

Background: AA provided a survival advantage compared to placebo, in pts who had received docetaxel for CRPC. Before the regulatory authority approval, AA was made available in Italy through a NPP supervised by the local ethic committees. The present retrospective study is aimed to assess PRE and CO in an unselected CRPC population which received AA by NPP. Methods: We retrospectively reviewed the clinical records of all pts treated with AA by NPP in our Institutions. For each pt we have recorded the pre and post-AA clinical history, the treatment details and outcomes. We have assessed the ability of a series of selected 22 clinical factors to predict AA response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 136 pts from 13 Italian hospitals. The median age was 72 yrs (range 52-87). The median baseline PSA was 154 ng/ml (range 0.33->100.000); 80% and 16.7% of the pts showed bone and measurable lesions respectively. The median duration of AA treatment was 15 wks (range 1-73); 59 treatments are ongoing. Grade 3-4 toxicities were anemia (5 pts), nausea (1 pt), fatigue (4 pts), bone pain (3 pts), and hypokaliemia (1 pt). A PSA reduction > 50% was observed in 37.5% of the pts. Having a performance status (PS) 0-1 [(exp(beta) 4.541; p= 0.018], a previous ormonotherapy lasting >40 months [(exp(beta) 3.299; p= 0.020], baseline hemoglobin >12 g/dl [(exp(beta) 2.595; p= 0.074], no visceral organ involvement [(exp(beta) 1.929; p= 0.097] resulted to be independently predictive of a PSA reduction > 50%. The median PFS and OS were 5 mos and 14 mos, respectively; the 1-year PFS and OS rates were 25.7% and 53%, respectively. Conclusions: Our preliminary results have confirmed the efficacy of AA in second line CRPC outside clinical trials. Pts with good PS, with good hemoglobin levels, with long-lasting hormosensitivity, and without visceral organ involvement have higher probability to achieve a biochemical response to AA.
Effect of suppression of bcl-2 with antisense oligonucleotides on p53 expression.
Authors: Guinan Patrick , Rubenstein Marvin , Hollowell Courtney M.P.
Published: March 2020

e16085

Background: In theory gene therapy is specific but difficulties are encounted in practice. Tumors express altered patterns of expression and regulatory pathways provide many targets. However the actual activity of most genes are similar to normal. Resistance develops because pathways are complex, regulated by stimulatory and inhibitory factors, each affected by therapy. Tumors alter dependence on targeted gene products for growth by relying upon others, through compensation. Antisense oligos have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. Cells treated with antisense directed against bcl-2 compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing androgen receptor (AR), (co-activating) p300 and IL-6 expression. This suggests that in LNCaP a progression to increased androgen sensitivity accompanies bcl-2 suppression with a pattern of co-activation associated with more advanced prostate tumors. Methods: We evaluated mono- and bispecific oligos which targeted and equally suppressed bcl-2 expression in LNCaP cells. To further evaluate compensatory mechanisms related to tumor resistance we evaluated the level of the suppressor gene p53 employing RT-PCR and agarose gel quantification. Bands representing pcr product were photographed, converted to black and white and assessed by MIPAV software. Results: Comparable amounts of RNA from LNCaP cells treated with either mono- or bispecific oligos directed against bcl-2 (and EGFR in the bispecifics) were evaluated by RT-PCR using primers directed against p53. When background intensity was subtracted, the relative intensity of all bands corresponding to p53 and representing cells treated with MR4, MR24 and MR42 (compared to controls) were respectively increased 47.5% ± 42.3 (p = 0.02), 86.5% ± 35.3 (p = 0.00013) and 58.0% ± 42.0 (p = 0.0077). These results were pooled from both duplicate PCR runs and gels, and indicate each oligo targeting bcl-2 significantly enhanced p53 expression. Conclusions: Inhibition of bcl-2 activity mediated via antisense oligos enhances suppressor gene p53 expression. In contrast to the effects noted above, p53 enhancement would appear beneficial.
The prevalence of cardiac risk factors in men with localized prostate cancer undergoing androgren deprivation therapy in British Columbia, Canada.
Authors: Rajala Jennifer , Tyldesley Scott , Pickles Tom , Virani Sean
Published: March 2020

e16086

Background: While androgen deprivation therapy (ADT) decreases the risk of prostate cancer specific mortality in high risk localized prostate cancer treated with radiotherapy, it worsens cardiovascular (CV) risk factor profiles in treated men. Patients with pre-existing traditional cardiac risk factors who are treated with ADT have a higher rate of CV mortality than patients without risk factors. Methods: We retrospectively reviewed the charts of the last 100 consecutive men with intermediate or high risk localized prostate cancer who were referred to the British Columbia Cancer Agency from October 1, 2011 to October 31, 2012 and treated with ADT. Inclusion criteria were referral to an oncologist within 3 months of diagnosis and a planned duration of ADT of 6 month or more. Patients with metastatic prostate cancer at diagnosis were excluded. Data on traditional cardiac risk factors were collected and a Framingham risk score was calculated on each patient to estimate their 10 year cardiac event risk. Results: The average age of the men referred for ADT was 71.7±7 years. Most, 70%, had poorly differentiated disease and the PSA was >10ug/L in 62%. An updated Charlson score of 0 was calculated in 82% of patients; only 4% had a score ≥2. The Framingham risk of a cardiac event in the next 10 years was calculated to be high (more than 20% risk) in 69%, intermediate (a 10-20% risk) in 30%, and low (<10% risk) in 1% of the patients. A history of coronary artery disease was present in 17 patients, 11 of whom had documented revascularization. Baseline type 2 diabetes or impaired glucose tolerance was present in 24 patients, and 58 patients had a history of hypertension. Lipid profiles had been measured within the past year in 38 patients, and 35 patients had a baseline ECG on the chart. Conclusions: Given the high prevalence of cardiac risk factors in men with prostate cancer referred for ADT, we recommend baseline cardiac risk screening of lipids, blood glucose, and blood pressure in these patients with subsequent close monitoring of these parameters while on ADT. Among those individuals with established or symptomatic CV disease, we recommend referral to a specialist with expertise in cardiology.
Association of Rs1139971, a KAI1 polymorphism, with bone metastasis progression in prostate cancer and ganglionnary metastasis.
Authors: Audouin Marie , Cancel Tassin Géraldine , Gaffory Cécile , Ondet Valérie , Oudard Stephane , Azzouzi Abdel Rahmene , Roupret Morgan , Cussenot Olivier
Published: March 2020

e16089

Background: Metastatic prostate cancer, with bones as principal location, is responsible for most of the death from this malignancy. If the molecular mecanisms of the metastasis progression are not completely solved, many involved pathways have been clarified. Association studies have proven that genetic factors could affect the risk of prostate cancer or its agressiveness. Likewise, some polymorphisms from genes involved in metastatic pathways could have a meaningfull function in the individual genetic susceptibility to metastatic prostate cancer. The KAI1 gene is known to be implicated in the metastatic process of many malignant tumors, such as breast, lung or colorectal cancer. Moreover, the protein encoded by this gene seems to act as a metastatic suppressor. In this study, we searched for an association between the risk of metastatic progression and a polymorphism from the KAI gene (rs1139971). Methods: It was a retrospective and multicentrique study, comparing 195 patients harbouring bone and/or ganglionnary metastatic prostate cancer with 386 patients affected by a non metastatic prostate cancer. All the patients were caucasians. The variant rs1139971 has been genotyped by Taqman technology. Results: The allele A from rs1139971 was found to be less frequent in metastatic patients but this result wasn’t significant. The patients were then stratified according to the metastatic location : bone or ganglionnary. In this case, the allele A was significantly associated with metastatic risk in the group of patients with bone metastasis [OR = 0,525 ; IC 95% = 0,332-0,828 ; p = 0,0056]. Conclusions: In this study, a significant association has been pointed up between bone metastatic prostate cancer and the polymorphism rs1139971 from KAI1 gene. However, these results need to be confirmed on a larger and independant population.
Potential predictive and prognostic factors for sequential treatment with abiraterone acetate and cabazitaxel in metastatic docetaxel-refractory castration-resistant prostate cancer (mDR-CRPC).
Authors: Bracarda Sergio , Hamzaj Alketa , Sisani Michele , Di Lorenzo Giuseppe , Marrocolo Francesca , del Buono Sabrina , de Simone Valeria , De Angelis Verena
Published: March 2020

e16093

Background: in recent years Abiraterone Acetate (AA) andCabazitaxel (Cbz) were shown to be efficacious agents in patients with mDR-CRPC. However, no data exist for patients treated with both these drugs in terms of best sequencing evaluation and potential predictive and prognostic factors for different treatment sequencies. Aim of our study was to analyze these data in a real world scenario. Methods: intention-to-treat (ITT) analysis of activity data deriving from all consecutive patients with mDR-CRPC treated in our unit with prednisone plus Cbz, AA or both drugs. Data analyzed were, median Progression Free Survival (mPFS) for the two single agents and their sequencies (evaluated according to PCWG2, Prostate Cancer Working Group 2, criteria) and their possible correlations with median age, Gleason score, baseline PSA, ECOG PS, visceral metastases and number of previous chemotherapy lines. Results: here we report characteristics and activity data of the initial 62 patients, 7 treated with Cbz, 32 with AA and 16 with both drugs. The median age of our study population was 71.5 years (range, 55-87), median Gleason Score 8 (4-9) and median ECOG PS 0 (0–3); visceral disease was present in 37 cases (59.7%). The mPFS, according to Kaplan Meier method (KM), was 4.7 months (m) for patients treated with Cbz, 8.6 months for cases treated with AA and 8.2 m for cases treated with both agents. Of the 16 patients treated with both drugs, 12 received a sequence Cbz-AA and 4 a sequence AA-Cbz for an overall median PFS of, respectively, 5.6 and 4.0 m. Any of the analyzed prognostic or predictive factor was found to be significant. Conclusions: in our experience AA and Cbz were showed to be effective agents in the mDR-CRPC setting also when used sequentially. No clear indication of a preferred treatment sequence was identified such as eventual prognostic/predictive factors, also because of the limited number of treated patients. These data should be analyzed in large size prospective trials.
Stereotactic hypofracionated radiotherapy for prostate cancer patients.
Authors: Rucinska Monika , Stefanczyk Marta , Minczewska Joanna , Nawrocki Sergiusz
Published: March 2020

e16097

Background: 3D conformal radiotherapy (78Gy in 2Gy per fraction) is the standard treatment for prostate cancer patients. It is a very long treatment, not comfortable both for patients and radiotherapy departments. Stereotactic radiotherapy has recently been recognized as an alternative technique. Prostate cancer has probably a low α/β ratio (1.5Gy) and 33.5Gy in 5 fractions has the predicted efficacy of 78Gy in 39 fractions. The objective of the study was to investigate the effectiveness and safety of stereotactic radiotherapy for localized prostate cancer. Methods: This is a prospective one-center clinical study. The treatment was done with IMRT. PTV received 33.5Gy in 5 fractions twice a week. Three gold fiducial markers were placed in the prostate under transrectal ultrasound guidance for image-guided positioning and motion tracking. Treatment planning CT and MRI scans were performed. IMRT plans were done. Before each treatment MV Cone Beam CT and portal imagines for markers were performed. Results: In this analysis 32 patients were included (age 65-83 years, median 73 years) with localized low- and intermediate-risk (according to NCCN) adenocarcinoma of prostate T2-T3N0M0. Combined Gleason scores were 5 to 7, the prostate-specific antigen (PSA) was 4.7-20.0ng/ml (median 10.2ng/ml). The median prostate volume calculated during treatment planning (on CT and MR) was 40.5cc (15.8cc to 113.6cc). Acute genitourinary toxicity Grade 1–2 was observed in about 50% patients and only Grade 1 acute gastrointestinal toxicity in 25% patients. No Grade 3 or higher toxicity was reported. Only 3 patients reported rectal bleeding after radiotherapy (Grade 1 late toxicity). PSA level were systematically decreased to 1.08ng/ml 3 months, 0.91ng/ml 6 months and 0.56ng/ml 9 months after treatment end. Conclusions: Stereotactic hypofractionated radiotherapy for prostate cancer patients is an effective and safe treatment in short term analysis.
The impact of FDG-PET/CT on the management of gynecologic cancers: A retrospective study.
Authors: Abu-Hijlih Ramiz Ahmad , Al-Ibraheem Akram , Abuodeh Yazan Asad , Jaradat Imada A.
Published: March 2020

e16500

Background: Fluoro-Deoxyglucose (FDG-PET) coupled with Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) provides valuable information in primary staging and evaluation of therapeutic response in gynecological cancer patients. The aim of this study is to investigate the additional value of PET/CT to MRI and CT scan, in patients recently diagnosed with a gynecological tumor or for evaluation of treatment response. Methods: Between January 2010 and June 2012, forty patients with gynecologic tumors (23 cervical, 8 endometrial and 9 ovarian) were evaluated at King Hussein Cancer Center. These patients were divided into two groups: (1) PET scan at presentation for initial staging workup (15 patients) and (2)PET scan at follow up for treatment response evaluation (25 patients). Results: The FDG-PET/CT scan yielded the following additional information: upstaging in 7.5% (3 in 40 patients) and down staging in 32.5% (13 in 40 patients). As a result, treatment strategy was changed from curative to palliative in one patient, and additional curative therapy was implemented following exclusion of distant metastasis in eight patients. Moreover, the discrepancy in nodal status found with FDG-PET/CT compared with anatomical imaging was detected in 8 patients (20%), which led to modifications in radiotherapy field and customizing the radiation dose with minimizing treatment-related toxicity. Conclusions: This study has demonstrated the effectiveness of FDG-PET/CT in the management of gynecological cancer patients. It is a highly valuable utility that raised the accuracy of patients’ stratification to curative or palliative treatments. Furthermore it helped radiotherapy to be more precisely targeted towards the malignant process. However, further prospective studies are still required to identify the group of patients who would benefit the most from this procedure.
Ovarian needle biopsy: A study of 84 cases with cytologic-histologic correlation.
Authors: Nagamine Kimberly , Terada Keith Y. , Shimizu David , Tauchi-Nishi Pamela
Published: March 2020

e16501

Background: Ovarian needle biopsy (ONB) is well tolerated and underutilized. It may be employed for preoperative diagnosis and to treat symptomatic benign cysts. There is reluctance to utilize this procedure due to potential cyst rupture or seeding of malignant cells. We studied the efficacy of ONB over an 11-year period at our institution. Methods: Between January 2000 and August 2012, we retrieved 134 ONB specimens from our database. One hundred sixteen (87%) were performed by obstetrician-gynecologists, 8 (6%) by radiologists, 4 (3%) by surgeons, and 6 (4%) by other clinicians. Results: Eighty-four (63%) cases had corresponding surgical specimens, 78 (93%) of which were obtained concomitantly. Ten (12%) cases were malignant and 74 (88%) benign (Table). Sensitivity and specificity of ONB were 70% and 100%, respectively. Forty-one (53%) were benign ovarian neoplasms, and 30 (39%) were cysts. Regarding malignant lesions, 8 (80%) were primary ovarian epithelial cancers. There was 1 granulosa cell tumor and 1 metastatic lung adenocarcinoma. Three false negative cases were noted; 2 serous borderline tumors and 1 mucinous cystadenocarcinoma. These were sampling errors; no diagnostic tumor cells were present in the aspirates. Conclusions: ONB may be effective in diagnosing and treating ovarian lesions. In our study, it was highly specific and sensitive, with the exception of borderline tumors. [Table: see text]
Predictability of later developed relapse in endometrial carcinoma in young women with functional imaging parameters of fes/FDG SUV ratio after fertility-sparing hormone treatment.
Authors: Yoshida Yoshio , Okazawa Hidehiko , Shinagawa Akiko , Kiyono Yasushi , Mori Tetsuya , Kurokawa Tetsuji
Published: March 2020

e16502

Background: Even in responders of fertility-sparing hormone treatment for uterine endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women, there have been high potential risks of later developed relapse. The aim of this study was whether changes in FDG and fluoroestradiol (FES) PET parameters following hormone treatment have the prognostic factor in prediction of later developed relapse. Methods: Eight young patients with EC and AH were treated by fertility-sparing treatment with a high-dose of medroxyprogesterone acetate (MPA) for 26 weeks. All patients underwent two FDG and FES-PET scans at baseline and 8 weeks after the beginning of MPA treatment, respectively. For each lesion, metabolic indices were calculated by standardized uptake values (SUV). All patients were followed up for 2 years. Values of FDG-SUV, FES-SUV and FES/FDG SUV ratio of tumors were retrospectively reviewed. The correlation between these parameters and clinical outcome of EC and AH for 2 years was evaluated. Results: An initial complete response was achieved in all patients. Two of 5 responders (40%) with AH and one of three (33%) responders with EC later developed (72-88weeks) relapse. One of those three patients underwent hysterectomy due to no response for additional MPA therapy. The tracer uptake of FDG and FES was decrease in all eight patients after 8 weeks. The FES/FDG ratio was increased in all three patients with later developed relapse, but the FES/FDG ratio was decrease in all patients without recurrence for 8 weeks. There was a significant difference of the change in FES/FDG ratio between later developed relapse patients and no relapse patients (0.113 vs -0.392; p = 0.044). Conclusions: This study suggests that an increase in the FES/FDG ratio after 8 weeks fertility-sparing hormone treatment with a high-dose of MPA may be a useful biomarker for predicting later developed relapse in EC and AH in young women.
Treatment of chemoresistant ovarian cancer with sigma2/SMAC and cisplatin.
Authors: Wilkinson-Ryan Ivy , Spitzer Dirk , Mach Robert , Vangveravong Suwanna , Goedegebuure Peter S , Hashim Yassar , Plambeck-Suess Stacey , Powell Matthew A. , Mutch David Gardner , Hawkins William G.
Published: March 2020

e16508

Background: Platinum resistance continues to be a major barrier to the successful treatment of ovarian cancer. Overexpression of the X-linked inhibitor of apoptosis proteins (XIAP) contribute to platinum resistance in ovarian cancer through inhibition of caspases and up regulation of Akt activity. Second mitochondrial-derived activators of caspases (SMAC) is an endogenous protein that binds to and reverses XIAP-mediated inhibition of caspases. In order to exploit the SMAC-mediated pro-apoptotic pathway pharmacologically, SMAC mimetics have been developed and shown to induce apoptosis in cancer cells in vitro and in vivo. Untargeted cytotoxic cancer drugs bind to both malignant and normal tissue leading to significant toxicity. We have shown previously that solid tumors upregulate the sigma-2 receptor. We have also shown that sigma-2 ligands are internalized into cancer cells and are therefore an appealing vehicle for tumor targeted therapy. The goal of this study is to test if a conjugate drug of sigma-2 ligand and a SMAC mimetic (sigma-2/SMAC) in combination with chemotherapy is capable of overcoming chemoresistance in ovarian cancer. Methods: SKOV3 and OVCAR3 ovarian cancer cell lines were treated with sigma2/SMAC (1-16μM) and/or cisplatin (.5-10μg/mL). Viability assays were used to detect cell death. Luminescence-based caspase assays were used to compare the activity of caspase-3, -7, and -9 between treatment groups to document involvement of the XIAP survival pathway. Results: We found that sigma2-SMAC is synergistic when used in combination with cisplatin. Compared to untreated cells, SKOV3 cells treated with sigma/2SMAC (4uM), cisplatin .5ug/mL, or combination therapy showed 52.6%, 117.7%, and 34.8% viability respectively (p<.05). Cisplatin and sigma2/SMAC remained synergistic at increasing doses. Similar results were observed in OVCAR3 cells. Caspase-3 and -7 increased in combination therapy 1.2-fold over Sigma/2SMAC alone (4uM) and 7-fold over cisplatin alone (.5ug/mL) in SKOV3 cells (p<.05). Conclusions: This study suggests that the sigma2/SMAC conjugate provides a targeted means for overcoming chemoresistance in ovarian cancer through inhibition of XIAP and activation of caspases.
Dose-dense first-line chemotherapy in advanced ovarian cancer: How to select the patients?
Authors: Tjulandina Alexandra , Stenina Marina , Pokataev Ilya , Fedyanin Mikhail , Tryakin Alexey , Tjulandin Sergei
Published: March 2020

e16509

Background: First line dose-dense (dd) regimens improve PFS in patients (pts) with advanced ovarian cancer, but also increase hematological toxicity, peripheral neuropathy and usage of G-CSF. Nowadays it is unknown which pts benefit from this treatment. Methods: The analysis included 156 pts with ovarian carcinoma stages Ic-IV, who received paclitaxel (Ptx) and platinum agents in first line chemotherapy (CT) from 1996 to 2010 in our center. Retrospective group contained 91 pts, who were administered standard regimens (Ptx 175 mg/m2 + Carboplatin (C) AUC5-6 /Cisplatin (DDP) 75 mg/m2 every 3 weeks). Prospective group included 65 pts. Forty of them received 9 cycles Ptx 150 mg/m2+DDP 50 mg/m2 every 2 weeks, 25 pts were given 6 cycles Ptx 80 mg/m21,8,15 days + C AUC6 every 3 weeks. Results: Median PFS in the dd (12.5 months) and the standard arms (13.3 months) were not statistically significantly different (p = 0.6, HR 0.9; 95% CI 0.61-1.37). Multivariate analysis revealed the optimality (p=0.006) and time (p = 0.008) of cytoreduction were found as the strongest factors exerted on PFS and could take effect on choice of CT regimen. Median PFS was longer in pts with primary optimal cytoreduction (26.3 months) than in group with primary non optimal, interval debulking or without any surgery treatment (10.9 months) (p < 0.0001, HR 0.28; 95% CI 0.23-0.55). The dd regimens prolonged PFS in comparison with the standard arm in pts with favorable prognosis (primary optimal cytoreduction): median was not reached vs 15.1 months respectively (p = 0.02, HR 0.36; 95%CI 0.13-1.2). Meanwhile, median PFS in unfavorable prognostic group was not different between 2 arms: 10.3 vs 11.5 months respectively (p = 0.4 HR 1.26; 95% CI 0.8-2.02). Conclusions: First-line dd statistically significantly prolong PFS in pts with primary optimal cytoreduction comparing with standard conventional CT. It is necessary to validate this predictive factor in prospective trial.
Peculiarities of clinical characteristics in different aged patients with vulvar cancer.
Authors: Ivanova Victoria Aleksandrovna , Nerodo Galina , Nerodo Ekaterina Alekseevna
Published: March 2020

e16512

Background: Comparison of vulvar cancer clinical flow in patients of reproductive and old age. Methods: The studying of vulvar cancer clinical delopment included 64 patients of reproductive age and 775 patients of old age. Results: The patients were from 20 to 90 years old; 64 (7.6%) of them were from 20 to 50 years old; the other 92.4% were more than 50 years old. The patients of reproductive age at early stages made up 70.3%; the patients of old age at early stages made up 70.3%. Hypertensive disease (13.5%), obesity (13.5%), diseases of liver and stomach (11.8%) and the sole case of diabetes mellitus (1.6%) were among the concomitant diseases of the reproductive age patients. Among the seniors,: hypertensive disease (77.7%), atherosclerosis (42.9%), obesity (62.8%), osteochondrosis (18.3%), diabetes mellitus (9.1%), diseases of liver and gall bladder (29.95%). Only 16% of the patients from the younger group had leukokeratosis and kraurosis; among the seniors, 62% had those diseases. At the same time, the younger the group of patients with vulvar cancer, the more often they had papilloma, condyloma on vulva in their anamnesis, and infection of human papilloma virus. In the group under 50 such patients made up 87.5%, and in the group of seniors there was one case of infection of human papilloma virus – 0.48%. All the patients undergone different types of complex curing; more than half of the patients undergone chemotherapy. 17% of the patients of the reproductive age, and 23.3% of the seniors had the relapses of the disease. Conclusions: Our study proved the statement about existence of two pathogenetic variants of vulvar cancer appearance: the first variant is HPV– positive, diagnosed in young women; the second variant is HPV– negative, diagnosed in women of elderly age, associated with neurodystrophic processes and chronic infection.