bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of addition of docetaxel (D) to hormonal therapy (HT) versus HT alone on quality of life: Results from a phase III study in non-metastatic high-risk prostate cancer (PC) patients (pts) with a rising PSA status.
Authors: Oudard Stephane , Gillaizeau Florence , Peyrard Severine , Latorzeff Igor , Beuzeboc Philippe , Sevin Emmanuel , Rolland Frederic , Mourey Loic , Priou Franck , Culine Stephane
Published: March 2020

e16009

Background: Around 75% of non-metastatic high risk PC pts undergo PSA recurrence within 2 years after local therapy. Effect of D in addition to HT on Quality Of Life (HRQoL) was assessed using QLQ-C30. Methods: HRQoL was assessed every 3months: baseline, 3m, 6m, 9m and 12m for this multicenter, randomized phase III study comparing arm A: HT+D (70 mg/m2 Q3W, 6 cycles) and arm B: HT (triptorelin) every 3m for 1 year in non-metastatic PC pts at high-risk of recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Stratification factors (SF) were RP vs RT and PSA-doubling time < or >6m. Inclusion criteria were at least 1 of: Gleason >8, PSA-DT <6m, positive surgical margins, PSA velocity >0.75ng/mL/year, pathological pelvic lymph nodes, time from RP/RT to inclusion < 12m. Primary endpoint was PSA PFS (ASCO2011, abs 84423); secondary endpoints: PSA response, time to metastasis, overall survival, QoL and safety. Treatment effect on QoL was analyzed using 1) linear (L) and non-linear (NL) mixed models with continuous and discrete time points from baseline to 12m. Covariates were: SF, an interaction term between time and treatment and 2) time to 20% degradation of QoL upon Cox regression model. Results: Included =254, ITT=251. Arm A (125) vs B (126): median age(y) 64 vs 66, time(m) initial diagnosis to inclusion 35 vs 34, ECOG=0: 96% vs 93%, Gleason score (%) >8: 32 vs 27, RP (%): 69.6 vs 71.4, RT (%): 37.6 vs 38.1, PSA-DT (%) <6m: 53.6 vs 53.2, respectively. At baseline, mean (SD) Global Health status was 76.8 (19.4) and 81.6 (16.9) for arm A and B respectively (p=0.10). Fatigue dimension score was different at 3M (p<0.0001). Upon linear and non-linear longitudinal analysis, addition of D to HT had no effect on QoL (L: p=0.29; NL: p=0.25). Time to 20% QoL degradation was not significantly different between the 2 arms (p=0.44). Conclusions: Addition of docetaxel to hormonotherapy at an early stage after local therapy in non-metastatic high-risk PC pts with a rising PSA status does not significantly impact QoL during the first 12 months.
The free hormone hypothesis: Correlation of decreases in PSA with free testosterone rather than total testosterone in men with advanced prostate cancer treated with GTx-758.
Authors: Matsumoto Alvin M. , Getzenberg Robert H. , Coss Christopher , Hancock Michael L. , Si Xuemei , Dalton James T. , Steiner Mitchell S.
Published: March 2020

e16015

Background: Androgen deprivation therapy (ADT) improves disease-free survival but disease progression is related, in part, to ineffective castration. The free hormone hypothesis states that the biological activity of steroid hormones is affected by its unbound (free) rather than its protein-bound concentration. Serum total testosterone (T) concentrations predominantly reflect the T bound to plasma proteins and do not accurately predict prostatic levels of T. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) were randomized to receive 1000 mg or 2000 mg GTx-758 daily or leuprolide as their initial ADT. Serum total T (mass spectrometry), free T (equilibrium dialysis), SHBG and PSA concentrations were measured. A second Phase II study (G20007) was performed in men (n=9) with CRPC who then received GTx-758 2000 mg daily. Results: Although both treatments reduced serum total T levels to < 50 ng/dL, leuprolide decreased them to a greater extent. However, GTx-758 caused greater reductions in serum PSA, suggesting that total T concentrations did not accurately reflect the suppression of androgen activity. Both dosages of GTx-758 reduced free T levels to a greater extent (mean of 0.7 and 0.4 pg/ml at day 60, and 0.4 and 0.4 pg/ml on day 90, respectively) than leuprolide (mean of 1.4 pg/ml on day 60 and 1.4 pg/ml on day 90; p values <0.03). Similar clinical results were observed in CRPC patients where GTx-758 daily resulted in a 71% decrease in %free T and clinically relevant PSA reductions in men maintained on ADT with LHRH agonists. As a result of adverse events at higher doses of GTx-758, the trial was stopped early. Conclusions: The ERα agonist, GTx-758, reduced the biologically active form of T, free T, to significantly lower levels than leuprolide. Reductions in PSA appeared to be more highly associated with changes in free T. These data provide compelling evidence to support the free hormone hypothesis and suggest that serum free T concentrations would provide a better measure of therapeutic efficacy in ADT than total T. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed. Clinical trial information: NCT01326312.
Detecting lower in addition to the highest Gleason score prostate cancer on core biopsy and the odds of upgrading at radical prostatectomy.
Authors: Phillips John G , Aizer Ayal A. , Chen Ming-Hui , Hirsch Michelle S. , Richie Jerome P. , Tempany Clare M. , Hegde John , Loffredo Marian , D'Amico Anthony Victor
Published: March 2020

e16026

Background: We evaluated the odds of upgrading at radical prostatectomy when a biopsy core with a lower Gleason score (GS) compared to the core with the highest GS was present (ComboGS) versus not at diagnosis and in a concurrent submission, test ComboGS in a validation data set on the endpoint of prostate cancer-specific mortality. Methods: The study cohort consisted of 134 men with clinically localized PC diagnosed between 4/08 and 9/11 using a 12-core prostate needle biopsy. GS at biopsy and RP were assigned by an expert genitourinary pathologist. Logistic regression multivariable analysis (Table) was performed to assess the impact that ComboGShad on the odds of upgrading at RP adjusting for known predictors of upgrading. Results: Of 134 patients, 46 (34%) were upgraded. Both increasing percent positive biopsies (ppb) (p < 0.001) and PSA level (p=0.001) were associated with an increased odds of upgrading, whereas ComboGSwas associated with a decreased odds of upgrading (0.18 [95% CI: 0.04-0.76); p = 0.02). Men whose ppb was ≥ 33% (median) were upgraded in 47% (28 of 60) versus 14% (3 of 21) of cases (p = 0.009) when ComboGSwas absent versus present. These respective estimates in men with a PSA ≥ 5.2 ng/ml (median) were 43% and 12% (p = 0.019). Conclusions: In men with clinical factors associated with upgrading namely, increasing ppb and PSA, ComboGSis a favorable prognostic factor associated with a high rate of downgrading (> 40%) and a low rate (< 15%) of upgrading. Adjusted odds ratios and associated 95% confidence intervals and p values representing the impact of clinical factors at diagnosis on upgrading at radical prostatectomy. [Table: see text]
Prognostic implications of serum crosslinked-n-terminal telopeptide of type I collagen (NTx) for patients with initial prostate carcinoma.
Authors: Jablonka Fernando , Wroclawski Marcelo L. , Fonseca Fernando L. A. , Szwarc Marcelo , Machado Marcos Tobias , Vitoria Webster de Oliveira , Del Giglio Auro
Published: March 2020

e16030

Background: NTx is a metabolite of type I collagen, the main constituent of bone matrix, which has been previously shown to be increased in patients with bone metastasis. We wanted to evaluate NTx role in sample PCa patients at diagnosis when most of them have no overt bone involvement. Methods: Men with a histologic diagnosis of PCa at diagnosis were included. Serum Ntx was measured serially every 3 months up to two years by ELISA with the osteomark NTx Serum kit. Results: 55 PCa patients with a median age of 67 years (51 – 83), 86% with stage I, 4% with stage II, 2% with stage III and 10% with stage IV were included. At entry median NTx was of 14.65 nM and it did not correlate with age, Gleason score or PSA but we observed a significant direct correlation with stage (p = 0.0094). With a median follow up of 23 months, at diagnosis, Seum Ntx correlated significantly with biochemical recurrence (p = 0.012) as did Gleason score (p = 0.00056), Stage (p = 0.012) and PSA (p < 0.0001). By multivariate analysis the only 2 independent variables significantly correlated with biochemical recurrence were PSA (p = 0.046) and NTx (p = 0.021). Conclusions: We conclude that Serum Ntx has potential prognostic value in PCa patients at diagnosis and may improve current prognostic models. These data stress the potential prognostic importance of bone metabolism biomarkers for PCa patients even in the absence of overt bone involvement. Supported by: FAPESP.
Incremental cost (IC) analysis of skeletal related events (SREs) among elderly men with stage IV metastatic (M1) prostate cancer (PCa).
Authors: Jayasekera Jinani , Onukwugha Ebere , Bikov Kaloyan A. , Mullins C. Daniel , Seal Brian S. , Hussain Arif
Published: March 2020

e16034

Background: Patients diagnosed with stage IV M1PCa are predisposed to SREs, such as pathologic fracture (PF), spinal cord compression (SCC) and bone surgery (BS). There is limited information in the literature regarding the ICs associated with SREs among stage IV M1 PCa patients. Methods: We analyzed patients aged 66+ yrs diagnosed with incident stage IV M1 PCa between 2000 and 2007 from the linked SEER-Medicare dataset. Five mutually exclusive SRE categories were created: PF only, PF+concurrent surgery (SRG), SCC only, SCC+SRG, and BS only. Patients with multiple SREs were excluded. A propensity score for the incidence of an SRE was estimated using a logistic regression model including baseline demographic and clinical variables, diagnosis year and SEER region. Patients with SREs (cases) were matched to those without SREs (controls), based on the propensity score. The date of SRE of a case was assigned to a matched control, and the 12 month pre- and post-SRE costs were calculated. A difference-in-difference method was used to estimate the ICs (post-pre) for cases vs. controls. The analysis was conducted from a US Medicare perspective. Results: Application of inclusion criteria resulted in 1,131 stage IV M1 PCa patients with SREs. The average age was 78 yrs and 12% were African American. Using the propensity score, 1,031 cases were matched with 1,031 controls and allocated to the following SRE groups: PF+SRG (n=134), PF only (n=143), SCC+SRG (n=40), SCC only (n=538) and BS only (n=176). The average IC per SRE was $30,548 (vs. controls). The most expensive SRE group was SCC+SRG with a total average IC of $62,412, followed by BS only ($37,554), PF+SRG ($35,520), SCC ($28,027), and PF only ($17,839). Inpatient costs were the major driver of ICs followed by physician/non-institutional provider and skilled nursing facility (SNF) costs. Conclusions: The ICs associated with an SRE are significant. The IC of an SRE varies by type of SRE and service category. [Table: see text]
Effect of immunization with Ii-key modified HER2 (776-790) peptide vaccine (AE37) on immunologic responses in prostate cancer patients.
Authors: Perez Sonia A. , Anastasopoulou Eleftheria , Pappou Efi , Tzonis Panagiotis , Bisias Stratos , Thanos Anastasios , von Hofe Eric , Papamichail Michael , Baxevanis Constantin N.
Published: March 2020

e16037

Background: We have shown that the AE37 vaccine (Ii-Key modified HER2(776-790) peptide) is safe and induces HER2/neu–specific cellular immune responses in patients with prostate cancer (Perez SA et al Clin. Cancer Res. 2010, 16:3495). We now present data from 4-year immunological assessments of prostate cancer patients who received AE37. Methods: Seventeen patients in a phase I study were given 6 doses of AE37 at monthly intervals and one additional dose a year after initiating treatment. Immunological testing to assess active versus suppressive immunity was conducted one month (intermediate-term immunomonitoring [ITI]) and 3 years (long-term immunomonitoring [LTI]) after the final dose of AE37. ELISPOT and proliferation assays were conducted to assess cytokine secretion and mitogenic response to antigen. DTH reactions were measured to assess in vivo immune response to antigen. All assays were conducted using native HER2(776-790) peptide (AE36). The percent Treg cells and ng/ml TGFβ were determined as markers for immune suppression. Results: Neither ELISPOT nor proliferation assays were statistically different at LTI compared to ITI. While clearly above pre-vaccine responses, the drop in DTH was statistically significant (p < 0.05). Similarly, the increase in Treg cells and circulating TGFβ was also statistically significant. An increase of >200 % in PSA-doubling time at any point during the study was observed in 6/17 patients, with 3 retaining this effect to 5 years. Conclusions: AE37 generates immunological memory associated with possible clinical efficacy in spite of Tregs and TGF-β levels returning at 4 years after being decreased for up to 6 months after initial AE37 vaccination. These results support further randomized testing of the AE37 vaccine. Clinical trial information: 2006-003299-37. [Table: see text]
Prediction of reclassification at repeat biopsy with [-2]proPSA during active surveillance for low-risk prostate cancer: Prospective longitudinal analysis of a Japanese multicenter study cohort.
Authors: Sugimoto Mikio , Hirama Hiromi , Ito Kazuto , Shiraishi Taizo , Kakehi Yoshiyuki
Published: March 2020

e16054

Background: Biomarkers that predict aggressiveness and tumor burden of prostate cancer are needed for patients who undergo AS. One of such candidates is [-2]proPSA. It has been reported that expression of [-2]proPSA is specific to prostate cancer and associated with grade and stage. The aim of this research is to evaluate the predictive ability of [-2]proPSA and its related parameters for the biopsy reclassification during AS. Methods: 13 institutions participated in the multi-center Japanese AS study (a prospective one-arm cohort study). 134 patients were enrolled in this study between January 2002 and December 2003. Inclusion criteria are as follows; (1) stage T1cN0M0, (2) age from 50 to 80, (3) serum PSA = 20 ng/ ml or less, (4) one or two positive cores per 6 to 12 systematic biopsy cores, (5) Gleason score = 6 or less and (6) maximum cancer involvement in positive core = 50% or less. We prospectively collected blood samples from patients who opted AS as an initial treatment. The serum samples were stocked frozen until testing. The patients who remained on AS for 1-year were recommended to undergo repeat biopsy. Reclassification was judged by a central pathologist who was also involved in the initial diagnosis at inclusion. Results: 67 patients underwent repeat biopsy at 1-year after AS. Biopsy reclassification was histopathologically found in 25 of 67 patients (37.3%). Table shows the patients’ backgrounds and the cutoff values of predictive variables at 90% and 80% sensitivity and specificity. p2PSA, %p2PSA and phi; (p2PSA/fPSA) × √(tPSA) levels at baseline and p2PSA and phi at 1-year after AS were significantly higher in the reclassification group than those in the non-reclassification group. At 90% sensitivity, the cutoff values of p2PSA, %p2PSA and phi at baseline were 12.52, 1.51 and 37.91 with a specificity of 23.81%, 26.19% and 26.19%, respectively. In both 90% and 80% sensitivity, p2PSA and its related parameters have higher specificity than PSA and its related parameters. Conclusions: [-2]proPSA and its related parameters could predict pathological reclassification in repeat biopsy during AS.
Apoptotic activity in patient serum while on an acai juice product in the setting of a slowly rising PSA.
Authors: Kessler Elizabeth , Su Lih-Jen , Lu Xian , Morales Diana , Chronister Nicole , Anduha Mary , Wacker Michael , Yang Xiaoping , Flaig Thomas W. , Glode L. Michael , Lam Elaine Tat
Published: March 2020

e16055

Background: For patients with a slowly rising PSA, the timing of androgen deprivation therapy (ADT) initiation is highly debated given the long term side effects. In this setting, numerous nutraceuticals, or plant derivatives, such as grape seed, milk thistle, or pomegranate have been shown to slow the growth of prostate cancer (PCa). The acai berry has been shown to be rich in flavinoids with high antioxidant properties and was evaluated in this phase II single-institution study in asymptomatic PCa patients with a rising PSA. The primary endpoint was decline in PSA of 50% from baseline. While flavinoids have been shown to induce cell cycle arrest, understanding the actions of the mix of phytochemicals has not been rigorously undertaken for the acai berry. It has shown proapoptotic effects in vitro on leukemic cell lines, and decreased cytokine production correlated with subsequent anti-esophageal tumorogenesis effects in vivo. In order to better understand the mechanism of action of acai, patient serum samples were analyzed in vitro. Methods: While on trial, patients consumed 2oz of acai juice product daily for 30 weeks. Two serum samples were drawn at weeks 0, 2, 6, and 18 for correlative analysis with the M30 Apoptosense ELISA. This measures caspase cleaved Keratin18 (ccK18) as a marker of early apoptotic activity. Results: An increase from baseline in ccK18 was seen at 2 weeks in a majority of patients (13/19; p= 0.12). Additionally, the one clinical responder on trial had a significantly higher level of ccK18 throughout the trial with a peak at week 6. Baseline ccK18 values did not correlate with clinical outcome (Spearman coefficient r=-0.13, p=0.6). Conclusions: Nutraceuticals may offer a well-tolerated treatment option for slowing the growth of prostate cancer as evidenced by the prolongation in doubling time in 86% of patients in this trial. The rise of ccK18 at week 2 and elevated levels in the responder’s serum suggest there is a pro-apoptotic treatment effect with acai. Additional cytokine analysis, and ratio of necrotic death to apoptotic death is underway in order to compare additional mechanisms. This initial evaluation offers early insight of the mechanism of action of acai in PCa.
Timing of PSA response to guide cessation of docetaxel in prostate cancer.
Authors: Dickinson Peter D. , Malik Jahangeer , Slevin Finbar , Sivanandan Ananth , Clarke Noel W. , Choudhury Ananya , Elliott Tony
Published: March 2020

e16069

Background: Docetaxel plus prednisolone is an established treatment for men with advanced prostate cancer. Clinicians need to be able to identify men who are not benefiting from chemotherapy, and a key unanswered question is how many cycles of docetaxel should men receive before this assessment is made. We investigated the prognostic significance of a PSA response to docetaxel chemotherapy and the number of cycles after which an absence of PSA response could reliably predict future non-response. Methods: Data was collected for men who received one to ten cycles of docetaxel for castrate refractory prostate cancer between 2005 and 2011. PSA was monitored during treatment. All men were treated at a single centre, The Christie NHS Foundation Trust, UK. Survival is defined as the interval between the first dose of docetaxel and the date of death. Results: Data was available for 320 patients. At the commencement of chemotherapy, median age was 67 years (range 49-81yrs) and median PSA was 207ng/ml. All patients had a Karnofsky Performance Status ≥ 70%. There were 239 deaths and the median survival of the whole group was 403 days. 140 (44%) patients received 6 cycles of docetaxel and 23 patients (7%) received 10 cycles. Median survival was significantly longer in men who had any fall in PSA during chemotherapy compared to those whose PSA did not fall (462 days vs 268 days, p<0.001). Any PSA fall occurred during the first 4 cycles of docetaxel for 95.1% of men. Median survival was significantly longer in men who had a 50% fall in PSA during chemotherapy compared to those who did not (491 vs 357 days, p<0.001). The 50% fall in PSA occurred during the first 5/6 cycles of chemotherapy in 91.5% and 97.7% of men respectively. Conclusions: A patient’s clinical condition is of paramount importance when assessing them during docetaxel chemotherapy. Our data suggest that a fall in PSA following docetaxel is an indicator of improved overall survival. PSA response could help clinicians decide when to stop docetaxel; patients are unlikely to have a fall in PSA if it has not occurred during the first 4 cycles of chemotherapy and they fall into a poor prognostic group. These patients should be considered for alternative treatment in order to improve outcomes and spare them unnecessary toxicity.
Quality of life in patients receiving herbal therapy for biochemically recurrent prostate cancer.
Authors: Beam Eric , Yang Dongyun , Ji Linyung , Quinn David I. , Groshen Susan G. , Pinski Jacek K. , Dorff Tanya B.
Published: March 2020

e16073

Background: Men who experience biochemical recurrence after curative therapy for prostate cancer are often treated with androgen deprivation therapy (ADT), though there is no proven survival benefit in this setting. Side effects of ADT negatively impact quality of life (QOL). There is interest in alternative therapies to control PSA without ADT side effects. In conjunction with clinical testing of prostate health cocktail (PHC), a combination herbal therapy for men with biochemically recurrent prostate cancer, we surveyed QOL in trial subjects who were still receiving PHC (n=11), or had moved on to ADT (n=12) or observation (n=16). Methods: Subjects were surveyed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, in which respondents report their level of physical and psychological functioning during the past 7 days. The survey was completed in person, by phone, by mail or via online submission. Results: Of the 40 men (93% of total trial subjects) who responded to the survey, the median age was 66 (range 54-84) and PSA was 2.8 (range 1.1-84). 23% had received radiation as primary treatment, 25% radical prostatectomy, and 52% had received both. One patient was receiving radiation at the time of survey and was excluded. In the Physical Well-Being domain, which assesses energy, feeling ill, nausea, pain and trouble meeting needs, there was a significantly lower score among men receiving ADT (median 25; 95% CI 23.5-26.2) compared to those taking PHC (26.5; CI 24.2-27.8) or being observed (28; 26.4-28) (p =0.006). There was no significant difference among the groups in the other domains, though within the Prostate Cancer-Specific Concerns domain significantly more men indicated they were "not at all" able to have/maintain erections in the ADT group (11/12) compared to PHC (6/11) and observation (5/15) (p=0.009). Conclusions: Decisions about treatment for rising PSA levels after curative-intent therapy must be informed by therapeutic value as well as consideration for QOL. We found that men being treated with ADT have a significantly lower physical function score, and the relatively high QOL for patients on a clinical trial of an herbal supplement was similar to that of patients being observed. Clinical trial information: NCT00669656.
Midterm oncologic outcomes after robotic-assisted laparoscopic radical prostatectomy.
Authors: Negron Edris J , Razmaria Aria , Ledezma Rodrigo , Richards Kyle A , Szmulewitz Russell Zelig , Zagaja Gregory
Published: March 2020

e16084

Background: The robotic surgery has been extensively adopted in many surgical areas, especially in Urology. It's proven benefits (less blood loss, shorter recovery and reduced complication rates) has made it the most popular method to perform a radical prostatectomy nowadays. However, scarce data exists on the long-term oncologic outcome of robotic assisted laparoscopic prostatectomy (RALP). Since 2003, over 3,000 RALPs have been performed at our institution. We report the midterm oncologic outcome data of 1,054 patients with a median follow up of 60 months after RALP. Methods: From March 2003 to August 2008, 1,054 patients underwent RALP. Prospectively attained clinical data has been stored in an IRB approved database. Follow up has been maintained every 6 months for 2 years, and yearly thereafter. Salvage RALPs were excluded. Biochemical recurrence (BCR) defined as PSA > 0.2ng/ml, disease free survival, cancer specific and overall survival were assessed. Results: Of the 1,054 patients within the database, 1,019 met the criteria for evaluation. Mean age was 60 years (IQR 55-65), and mean BMI 27 kg/m2 (IQR 25-30). 181 patiemts (17.3%) were African Americans. Pre-operative mean PSA was 5.3 ng/ml (IQR 4.2-7.4). The majority of patient's clinical stage was T1c [ 776 (73.6%)] while 278 were T2. Biopsy Gleason score (GS) was 6, 7, and ≥8, in 666 (63.2%), 324 (30.7%), and 64 patients (6.1%), respectively. 298 patients underwent a bilateral pelvic lymph node dissection (28.3%). Pathologic GS was 6, 7 and ≥8, in 563 (53.5%), 431 (41%), and 58 patients (5.5%), respectively. The pathological tumor stage was T2 in 834 (79.3%), T3a in 164 (15.6%) and T3b in 54 (5.1%). 14 patients (1.3%) had nodal involvement. Positive surgical margins occurred in 205 cases (20%). BCR occurred in 123 patients (12%). 2 deaths due to prostate cancer (0.2%) and 7 due to other causes (0.7%). Cancer specific survival is thus 99.1% at the mean follow up (60months) by Kaplan Meier analysis. Conclusions: Our midterm oncologic outcomes are consistent with those previously reported in open radical prostatectomy series. Ongoing, long term follow up is necessary in order to solidify it's role in prostate cancer managment.
Impact of news drugs in the median overall survival of patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Chaumard-Billotey Natacha , Chabaud Sylvie , Boyle Helen Jane , Favier Bertrand , Devaux Yves , Droz Jean-Pierre , Flechon Aude
Published: March 2020

e16096

Background: In the past 3 years new therapies, such as cabazitaxel (C): a novel taxane, enzulatamide (E): a new androgen receptor signaling inhibitor and abiraterone acetate (A): an inhibitor of androgen synthesis, have been developed in the treatment of post-docetaxel metastatic CRPC patients. This study assessed the clinical impact of these new drugs, comparing the outcomes of two historical cohorts of patients with mCRPC. Methods: We retrospectively reviewed the data of all patients with mCRPC treated by first line chemotherapy with docetaxel (D) at the Centre Léon Bérard. Based on the timing of the development of new drugs, we defined two cohorts based on two time periods depending on drugs available on the market: group 1: 2006-2009 corresponding to the period when only conventional drugs (D, mitoxantrone) were available; group 2: 2009-2012 corresponding to the period when new drugs like C, E, A could be used post docetaxel. Outcome evaluated was overall survival (OS). OS was defined as the time from date of D introduction to date of death or date of last follow-up for patients alive at last contact. Survival distributions were estimated by the Kaplan-Meier method and compared between groups using Log-Rank test. Results: One-hundred and thirty five patients were included: 66 patients in group 1 and 69 patients in group 2. Median age was 64 years in both groups. Karnofsky score was ≥ 80% for 67.7% of patients in group 1 and 81.8% in group 2. Gleason score was ≥ 9 for 38.7% and 31.4% of patients, respectively. In group 1, 47% of patients had visceral metastases when started on chemotherapy vs 40.6% in group 2. The weekly schedule of D (25mg/m2) was significantly more frequently used in group 1 than in group 2 (53% vs 15%, p<0.001). Median cumulative doses of D at first line treatment were significantly higher in group 2: 643 mg/m2 vs 454 mg/m2 (p<0.001). Median overall survival was 10.6 months (95% CI 7.8–15.7) in group 1 vs 32.5 months (95% CI 25–42.4) in group 2 (p<0·0001). Conclusions: This study reflects how the management of mCRPC patients has evolved over the last 7 years. Survival has improved especially through an earlier management, a more intensive schedule of D and the impact of these new drugs.
Low doses of ketoconazole and prednisone in patients with castration resistant prostate cancer (CRPC): A retrospective study on 73 patients.
Authors: Amaniera Gloria , Ballatore Valentina , Ruatta Fiorella , Prati Veronica , D'Urso Leonardo , Muto Giovanni , Aglietta Massimo , Ortega Cinzia
Published: March 2020

e16099

Background: The management of rising PSA in metastatic CRPC remains controversial. In Italy, abiraterone and enzalutamide are not at all approved in this setting of patients (pts). Ketoconazole is an inhibitor of adrenal androgen synthesis that has shown anti-tumor activity by interfering with C-17,20-lyase and could be used as secondary hormonal manipulation. In this retrospective study we report our experience with low doses of ketoconazole and prednisone in the treatment for CRPC. Methods: From March 2007 to March 2012, 73 pts with progressive CRPC who were previously treated with maximal androgen blockade received 200 mg ketoconazole orally 2 times daily, orally replacement prednisone (5 mg bid) and maintained LHRH-agonists. Overall, 40/73 (55%) pts had only bone metastases, 13/73 (18%) had nodal metastases, 20/73 (27%) both. Pts were monitored clinically and with serial PSA measurements every month. Partial biochemical response (PR) was defined as a >50% fall in PSA from baseline. Progressive disease (PD) was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. The endpoints of the study were biochemical response (BR), progression free survival (PFS), overall survival (OS) and adverse events assessment. Results: Median age was 74 (70-78) years; median baseline PSA was 33.09 (1.18-1348.8) ng/ml; median duration of the treatment was 5.05 (0-56.8) months. Twenty out 73 pts (27%) showed a decrease in PSA >50%, with a median duration of PSA response of 3.56 (1.17-33.58) months and 3 pts (4%) a PD. Fifty out 73 pts (68%) achieved a SD with an overall disease control (PR+SD) of 85%. PFS was 10 months for pts who achieved PR and 4 months for those with SD. Differences in PFS stratified according to site of metastases showed better prognosis in patients with only lymph nodes disease (p<0.05). Treatment with Ketoconazole was well tolerated and grades 3-4 toxicities occurred in only 3% of patients. Conclusions: Low-dose ketoconazole is an effective and well-tolerated treatment in pts with CRPC and should be considered in the subset of pts with low tumor burden and a rising PSA level despite maximal androgen blockade.
Prostate cancer survival at Oncologos del Occidente from Colombia, South America.
Authors: Salazar Piedrahita Hernan Dario , Villegas Mejia Carlos Raul , Chacon Cardona Jose Arnoby , Sanchez Villegas Tomas
Published: March 2020

e16102

Background: Prostate cancer occupies the first place in USA and the sixth in developing countries. In our records is the seventh and the second as general attention and mortality cause on men. Methods: A descriptive analysis of patients attending and treated at Oncologos del Occidente a Private Cancer Center was developed with 404 cases from January 2007 to June 2012. Results: Age mean 69.161 (Range 49-92 SD.8.614), 54% under 70 and 36% 70-80 years old; 56% Stage II and 0.7% unknown stage, 39% with Gleasson score under 6, 35% of Gleasson 7 and 25% with 8-10; PSA mean 41.394 (Range 0.002-900, SD.81.380) with 33% with PSA 4-10 and 24% with PSA of 10-20 ng/dl and 14% over 100; 64% without previous treatment; mean Previous Symptoms in months 6.002 (Range 1-120 months SD.11.901) with 75% under 3 months of symptoms; 90% of patients with Karnofsky over 80%; 29% relapsed and 56% of them biochemical relapsed; 75% of patients without any surgery and 17% Radical prostatectomy; 60% Radical radiation only to the prostate and 15% because of metastases and 9% because of post-Surgery cause; 34% with T1c; survival to 5 and 10 years about many prognosis factors are shown in the Table. Conclusions: This is the first effort in a specific area from Colombia related to general survival to 5 and 10 years based on prognosis factor and the results are similar to others experience centers. [Table: see text]
Clinical research on radiotherapy at different time for unresectable cervical cancer.
Authors: Li Wenhui , Chang Li , Ju Yunhe , Jiang Meiping , Li Lang , Wang Li , Liu Yanyou , Wang Yuhui , Jiang Zhou , Xiao Jing , Wang Zhengrong
Published: March 2020

e16516

Background: Radiotherapy is one of the mainstay treatments for cervical cancer. Circadian rhythm can be associated with cancers. In this study, we focused on the therapeutic effects, acute radiation damages and expressions of circadian genes in unresectable cervical cancer irradiated at different time. Methods: A total of 67 patients of unresectable cervical cancer (stage IIB-IIIB) were randomized to morning (9:00-11:00am) and evening (9:00-11:00pm) irradiation groups. Patients were treated with external beam radiotherapy to the whole pelvis (50 Gy in 25 fractions) and brachytherapy (36-42 Gy in 6-7 fractions). Therapeutic effects and acute radiation toxicities were evaluated after radiotherapy. Samples analyzed by flow cytometry were obtained from cervix at 9:00-11:00am and 9:00-11:00pm before and after radiotherapy. Results: Of 65 patients, the overall and higher grade of diarrhea (III-IV) induced by radiation in patients after morning vs evening radiotherapy were 75.0% vs 57.6% (p = 0.138), 12.5% vs 6.1% (P=0.427). Higher grade of hematologica toxicity in evening group was significantly increased as compared with morning group (54.5% vs 21.9%. p = 0.007). But patients’ response to radiation in two groups was similar (p = 0.708). Increased cell apoptosis and decreased G2/M phase fraction were observed significantly both in two groups after radiotherapy, but the increased/decreased values between two groups were found not to differ significantly. Expressions of circadian genes Per1, Per2 and Clock also increased after radiotherapy, and the increased levels between two groups were similar. Moreover, there were significant negative correlations between expressions of circadian genes Per1, Per2, Clock and G2/M phase fraction. But their expressions were positively correlated with cell apoptosis. Conclusions: Circadian genes may be associated with the similar radiation response and different toxicity in cervical cancer irradiated at different time by influencing cell cycle and apoptosis. The knowledge may provide a possibility of treating the patients with increased effect and decreased toxicity. Clinical trial information: ChiCTR-TRC-10001228.
Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).
Authors: Trillsch Fabian , Ruetzel Jan David , Herwig Uwe , Doerste Ulrike , Woelber Linn Lena , Grimm Donata , Choschzick Matthias , Jaenicke Fritz , Mahner Sven
Published: March 2020

e16535

Background: Surgery is the central aspect of clinical management in patients with borderline ovarian tumors (BOT). As patients have excellent overall prognosis after successful surgery, perioperative morbidity is a critical point for decision regarding the primary surgical approach. Methods: Clinical and surgical parameters of patients undergoing surgery for primary BOT at two gynecologic cancer centers between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparoscopy vs. laparotomy). Results: A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Primary laparoscopy was often performed with diagnostic intention and resulted in complete surgical staging in only 9.1% with subsequent formal indication for re-staging procedures. In contrast, complete surgical staging was achieved in 47.5% at primary laparotomy (p < 0.001). Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Conclusions: Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy should be considered as the preferred surgical approach for staging of patients with BOT if this appears feasible in preoperative evaluation.
Human papillomavirus (HPV) in young patients with head and neck squamous cell carcinoma.
Authors: Ungtrakul Teerapat , Keelawat Somboon , Vinayanuwattikun Chanida , Sriuranpong Virote
Published: March 2020

e17004

Background: HPV-associated head and neck squamous cell carcinoma (HNSCC) seems to increase during the last decades and has been commonly described to associate with younger patients. However the true prevalence of HPV in this specific population remains unclear. Methods: We collected archival 56 paraffin-embedded tumor tissue samples from HNSCC patients diagnosed and treated at King Chulalongkorn Memorial Hospital between 2000 and 2010. The major inclusion criterion was the age at diagnosis less than 45 year-old. HPV status was determined by HPV polymerase chain reaction (PCR) with degenerated primer covered over 37 HPV serotypes including high-risk HPV6, 11, 16, 18, 31 and 33. Additional immunohistochemical stain (IHC) of p16 was performed. The clinicopathological correlations with HPV status were analyzed. Results: Fourteen (25%) of the 56 HNSCC samples exhibited HPV DNA by PCR. Among cancer sites, 7 of 23 (30%) oral cavity, 3 of 11 (27%) oropharynx, and 4 of 22 (18%) hypopharynx and larynx primary organs displayed HPV DNA in tumor tissues. There was no major difference in the demographic data, tumor characteristics and treatment modalities between HPV DNA-negative and HPV DNA-positive samples. HPV DNA-positive tumors tended to have a better 2-year overall survival when compared with HPV DNA-negative tumors (66 and 40 percent, respectively) (p=0.10). After adjusted for independent prognostic variables of cigarette smoking, alcohol consumption, site of primary tumor and nodal status, only HPV DNA status was a predictor for a better survival (HR 0.16; 95%CI, 0.01-0.66). Additional IHC for p16 expression revealed 8 of 48 (16%) of p16 overexpression with twenty-two percent concordant rate with HPV PCR. Conclusions: Though HPV genome was moderately found in our young HNSCC patients, HPV DNA was not associated with a significant better survival in the primary analysis. Nevertheless, multivariate analysis adjusting for prognostic variables demonstrated a significant better prognosis in HPV DNA-positive tumors in this subset of HNSCC. Low concordant rate between HPV DNA and p16 overexpression in these young populations may caution the use of p16 overexpression as a surrogate marker of HPV.
Timing and severity of skin-related adverse events in a phase II trial of sorafenib (BAY43-9006) in patients with advanced thyroid cancer.
Authors: Terry Raya D. , Keefe Stephen Michael , Grande Carolyn Marie , Zifchak Larisa , Brose Marcia S.
Published: March 2020

e17009

Background: We previously conducted a phase II study of sorafenib (BAY43-9006) in advanced thyroid cancer. Rash and Hand-Foot Skin Reaction (HFSR) were two of the most common adverse events (AEs). Because these skin-related AEs affect quality of life, we further explored their time course and management. Methods: Fifty-five patients were treated on UPCC 03305, a phase II study of sorafenib in patients with advanced thyroid cancer from 2006 to 2011. AEs were recorded using CTCAE v.3.0 and reported here if relation to the drug was deemed “possibly-related” or greater. Cycle length was four weeks. Results: No grade 4 or 5 skin toxicity was observed. Forty-nine patients (89%) experienced rash. Thirty-one patients had a maximum severity of grade 1 (56%), eight had grade 2 (15%), and nine had grade 3 (18%). Fifty patients (91%) had HFSR. Thirteen patients had a maximum severity of grade 1 (24%), 33 had grade 2 (60%), and four had grade 3 (7%). The severity of rash peaked at cycle 1 (19% grade 2,3) and declined by cycle 3 (4% grade 2,3). The severity of HFSR peaked at cycle 2 (39%, grade 2,3) and declined by cycle 6 (10% grade 2,3). The timing and severity of rash and HFSR by cycle are reported in the Table. Following cycle 12 the severity and prevalence of skin AEs reached a steady state. Of the 55 patients, 30 patients (55%) required dose-reduction, and nine of those patients (31%) resumed full dose by the end of study date. Nine patients (16%) were dose-reduced for rash, 17 patients (31%) were dose-reduced for HFSR, and three patients (5%) were dose-reduced for both rash and HFSR. Conclusions: The severity of skin toxicity peaked by cycle 1 for rash and cycle 2 for HFSR. The severity improved dramatically for rash by cycle 3 and for HFSR by cycle 6. Our data support the close supervision of skin-related AEs in the first six cycles of treatment with sorafenib. However, the sustained high prevalence of rash and HFSR requires all patients receive ongoing skin care for the duration of therapy. Clinical trial information: NCT00095693. [Table: see text]
Identification, characterization, and chemotherapy utilization in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) using real-world data: Retrospective U.S. claims database analysis.
Authors: Flaig Thomas W. , Mehra Maneesha , Stellhorn Robert , Ng Yvette , Todd Mary Beth
Published: March 2020

e17510

Background: Limited data are available characterizing the progression of newly diagnosed PC to mCRPC and the use of different treatments in the mCRPC population. Real world longitudinal pt-level data were used to define, profile, and characterize treatment of pts with mCRPC. Methods: The PharMetrics database (2000-2011), a nationally representative, nonpayer–owned, integrated, commercial US claims database, was used to identify pts with an index PC diagnosis (dx) (ICD-9 codes 185.x or 233.4) and confirmation of ≥ 3 PSA test values in their claim history (n = 7402). An algorithm was developed to identify progression of PC from index dx to mCRPC by 1) evaluating the presence or absence of a secondary malignancy dx (ICD-9 codes 198.5, 199.1, and 198.82) to determine metastatic status, and 2) evaluating PSA increases with concurrent medical/surgical castration to determine castration-resistant status (Alemayehu et al, J Med Econ. 2010;13:351). Results: Mean follow-up duration was 50.7 ± 35.5 (SD) months. 271 pts (3.7%) had PC with metastases (mets) at dx. 2836 (38.3%) had medical/surgical/both castration during follow-up. 779 (11%) pts developed CRPC and 299 (4.0%) were defined as having mCRPC. Median age at PC dx and mCRPC dx was 73.5 and 76.7 years, respectively. Duration from initial PC dx to mCRPC was 28 ± 20.7 (SD) months. Prior to mCRPC dx (> 3 months), < 10% of pts were exposed to chemotherapy. Chemotherapy exposure (docetaxel, vinorelbine, estramustine, mitoxantrone) upon mCRPC dx (±3 mos) was 24%. Any docetaxel exposure after mCRPC dx was 42.8% (excluding pts with dx/follow-up pre-2004 docetaxel approval year). Other treatments in mCRPC pts at dx included opioids (n = 174, 58%) and bisphosphonates (n = 58, 19%). Conclusions: This effort identifies a methodology of using a retrospective US claims database to identify mCRPC, which accounts for less than 5% of pts with PC. 24% of pts presented with mets at initial PC dx while 76% developed mets over time. The moderate rate of opioid use and incomplete penetration of chemotherapy in mCRPC emphasizes the need for improved treatment alternatives.
Febrile neutropenia with adjuvant docetaxel and cyclophosphamide (TC) chemotherapy for breast cancer.
Authors: Yu Joanne Linda , Kurin Michael , Pasetka Mark , Sridhar Srikala S. , Warner Ellen
Published: March 2020

e17523

Background: The combination of docetaxel and cyclophosphamide (TC) for adjuvant treatment of early stage breast cancer has been shown to improve overall survival compared with doxorubicin and cyclophosphamide (AC) (Jones et al., 2006). Although cardiotoxicity is avoided with TC, the risk of febrile neutropenia (FN) is higher. For TC, reported rates of FN without prophylactic G-CSF range from 5% in the phase III trial to as high as 50% in retrospective chart reviews. As G-CSF is not covered by our provincial cancer funding agency for primary prophylaxis of FN with TC chemotherapy, we sought to determine the incidence of FN with TC chemotherapy in two comprehensive cancer centres in Ontario, Canada. Methods: Patients who received adjuvant TC chemotherapy between January 1, 2008 and December 31, 2012 were identified through the pharmacy databases. Electronic charts were retrospectively reviewed to abstract patient characteristics, treatment details including G-CSF use, and incidence of FN. Results: Preliminary results from one institution demonstrate that 187 patients were treated with TC over the study period. Of the 74 (40%) patients who did not receive primary G-CSF prophylaxis, 23 (31%) developed FN requiring hospitalization and treatment with intravenous antibiotics. However, none of the 113 patients who received primary G-CSF prophylaxis (funded by the patient or a third party payer) developed FN. Putative risk factors for FN in the absence of G-CSF including age, BSA, BMI, and pre-treatment absolute neutrophil count were examined and will be reported. Conclusions: The FN rate associated with TC chemotherapy exceeds 30%, higher than that reported in the clinical trial. As per ASCO guidelines, primary G-CSF prophylaxis should be given with TC chemotherapy, and in Canada this should be covered by provincial cancer funding agencies.
The use of molecular profiling (MP) beyond standard panels in day-to-day practice: A multi-institutional multinational survey.
Authors: Lemech Charlotte Rose , Newmark Joshua , Arkenau Hendrik-Tobias
Published: March 2020

e17532

Background: The complexity and associated cost of MP in cancer care is rapidly increasing and there are challenges as to its incorporation and utility in day-to-day oncological practice. Methods: A structured survey was sent to 42 institutions in Europe, USA and Asia-Pacific with well-established experience in basic oncology research and drug development. It aimed to gain insight into the frequency of MP beyond standard testing. The results from an 8 week snap-shot period were collated. Results: 42 medical oncologists, 5 radiation oncologists and 4 haematologists from 31 institutions responded; 41 from academic/teaching hospitals, 7 from the private sector and 3 from general hospitals. 26 respondents indicated that MP beyond standard panels was regularly performed. Testing was covered by public funding (38%), grants (35%) or private insurance/self pay (25%) and was performed for the purpose of research, diagnostics and other reasons (48, 47 & 5%, respectively). Gene analyses included DNA/RNA sequencing alone (11%) or in combination with IHC/FISH (38%), gene expression profiling (19%) and/or proteomics (8%). MP analysis was performed on state-of-the-art sequencing platforms (Sanger in 12%, a combination of Sanger and next generation sequencing (NGS) in 35% and NGS alone in 15%). Archived (60%) and fresh frozen biopsies (40%) were analyzed with a turnaround of <1 week (23%), between 1-3 weeks (66%) and >3 weeks (11%). 66% of results were discussed in a multidisciplinary meeting. Biobanking was available in 48% institutions with bioinformatics support available in 29%. The main challenges identified were funding and associated costs, incorporation of bioinformatics, data quality and staying abreast of new technologies. Conclusions: The use of MP beyond standard panels is increasing in both complexity and availability. Mastering clinical accessibility, data volume, and technical innovation will be key to incorporate MP in day–to-day practice.