bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma IL-8 and PD-L1 and overall survival in metastatic castration-resistant prostate cancer patients (mCRPC).
Authors: Polimera Hyma Vani , Pomerantz Mark , Leitzel Kim , Farah Subrina , Xie Wanling , Steinharter John A. , Shaw Grace , Ali Suhail , Drabick Joseph J. , Pancholy Neha , Menon Harry , Bartock Matthew Tyler , Shah Neal , Moku Prashanth Reddy , Maddukuri Ashok , Halstead E. Scott , Umstead Todd , McKeone Daniel , Spiegel Howard , Lipton Allan 
Published: May 2020

e17565 Background: We previously reported the significant prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 breast cancer serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced overall survival (OS) to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). Here we correlated plasma IL-8 and PD-L1 levels with OS in mCRPC patients. Methods: 201 metastatic CRPC patients had EDTA plasma available for this retrospective analysis. Patient eligibility included chemotherapy-naive mCRPC patients. The ELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate plasma IL-8 and PD-L1. Cox regression assessed hazard ratio (HR) for OS using both categorical (median) and continuous (log-transformed) biomarkers. Results: In univariate analysis, higher plasma IL-8 levels were significantly associated with reduced OS when analyzed as a continuous variable (HR = 1.53; p = 0.003) and were of borderline significance at the median cutpoint (HR = 1.32; p = 0.069; 20.9 vs 31.5 mos median OS). Plasma PD-L1 levels were not significantly associated with OS when analyzed as a continuous variable (p = 0.17), but increased levels were significant when analyzed at the median cutpoint (HR = 1.36; p = 0.044; 21.9 vs 29.0 mos median OS). When plasma IL-8 and PD-L1 levels were combined (median cutpoints), plasma IL-8 high / PD-L1 high patients (n = 58) had a significantly shorter OS vs the plasma IL-8 low / PD-L1 low patients (n = 58) (HR = 1.69; p = 0.009; 19.3 vs 32.9 mos median OS, respectively). In multivariate analysis, when adjusted for biopsy Gleason score, age, PSA, and ECOG PS (all at time of blood draw), only high plasma IL-8 (on a continuous basis) was significantly associated with reduced OS (HR = 1.43; p = 0.019). Conclusions: In mCRPC patients, high plasma IL-8 and PD-L1 levels were associated with reduced OS (separately and combined). Circulating IL-8 and PD-L1 evaluation may inform prognosis in mCRPC and could be considered as biomarkers in future studies determining response to immune checkpoint inhibitor and anti-IL8 therapy.
The study of the treatment efficacy in metastatic castration-resistant prostate cancer of low dose abiraterone with food.
Authors: Makphanchareonkit Kanta , Dejthevaporn Thitiya Sirisinha , Muntham Dittapol , Chansriwong Phichai 
Published: May 2020

e17571 Background: Abiraterone acetate and prednisolone (AAP) + ADT has been approved for treatment metastatic castration-resistant prostate cancer (CRPC) in the standard dose 1,000 mg with fasting state. Data in Ramathibodi hospital showed patients who had treated with standard dose of Abiraterone acetate (AA); had PSA response 47.83%. Previous studies showed using low dose AA of 250 mg with food had the non-inferiority results in efficacy. AA was not be reimbursed in Thailand, so the ability to use a highly effective drug at a quarter of the dose, could help in patient accessibility to cancer treatments. We sought to test the hypothesis that low-dose AA with food would have the comparable activity in Thai CRPC patients in both of the pre-Docetaxel and post Docetaxel treatment groups, and exploring the quality of life (QOL) of these patients. Methods: An observational cohort enrolled newly diagnosed metastasis CRPC at Ramathibodi hospital from 1st Jan 2019 to 31st Dec 2019. Patients were assigned to AA (250mg) with actual daily life meal. We collected the data of serum PSA and the adverse events every 4 weeks for 4 months. The QOL data was collected with the EuroQoL (EQ-5D) questionnaire which were done at baseline and every 4 weeks. The primary end point was PSA response that defined as PSA decreased ≥ 50% from PSA level at baseline. The secondary endpoint were the depth of PSA change, QOL and adverse events by using Fisher's exact test and T-test. Results: 21 patients were enrolled. At 12 weeks, there were 11 patients (52.38%) achieved 50% PSA response and 6 patients (28.57%) achieved 90% PSA response. The adverse events occurred 23.8%, and mostly were mild grade. The adverse events were comparable with the historical data in standard dose of AA. Low dose AA has significantly shown the improvement in quality of life from baseline (p < 0.001), and especially the significant improvement in pre-Docetaxel subgroup. Conclusions: Low-dose AA with food has good efficacy in PSA response, adverse events and QOL. Moreover, low dose AA shows more efficacy especially in pre-Docetaxel mCRPC patients. Low dose AA may be helping in reducing cost of cancer care, enabling in delivering affordable cancer care and increasing value of treatment.
Phase II study of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with previously-untreated, metastatic, prostatic adenocarcinoma.
Authors: Byeon Seonggyu , Kim Hana , Kim Hongsik , Jeon Hwang Gyun , Jeon Seong Soo , Lee Hyun Moo , Park Se Hoon 
Published: May 2020

e17580 Background: To evaluate the efficacy and safety of biweekly docetaxel (bD) plus androgen-deprivation therapy (ADT) in metastatic castration-naïve prostate cancer (mCNPC). Methods: This was an open-label, prospective, single-arm phase II trial. 42 patients with mCNPC were treated with docetaxel 40 mg/m2 every two weeks plus ADT. The primary end point was one year castration-resistant prostate cancer (CRPC)-free survival rate and the secondary end points were prostate-specific antigen (PSA) response, time to CRPC and safety. Results: Most patients (87.5%) had Gleason score 8 or more. The median value of PSA at initial treatment was 66.9 ng/ml (range 0.04 to 2339). After bD plus ADT, 39 patients (92.9%) had a PSA response (reduced PSA level 50% or more). The time to CRPC (one-year CRPC free survival 73.6%) and the duration of PSA response (18 months response 80.4%) did not reach the median. The bD plus ADT regimen was well-tolerated. The most common adverse events included neutropenia, nail changes and diarrhea. Conclusions: bD plus ADT treatment demonstrated favorable treatment outcomes with tolerability. Clinical trial information: NCT03061643 .
Pre-therapy visceral metastases in castrate resistant metastatic prostate cancer: Role in tumor progression.
Authors: Ruchalski Kathleen , Kim Hyun J. , Douek Michael , Raman Steven , Patel Maitraya , Gutierrez Antonio , Levine Benjamin D. , Fischer Cheryce , Auerbach Martin S. , Gupta Pawan , Coy Heidi , Villegas Bianca , Goldin Jonathan 
Published: May 2020

e17586 Background: Visceral metastases in castrate resistant metastatic prostate cancer (mCRPC) are known to develop late in the course of disease and portend a poor prognosis. As patients with visceral metastases still derive a clinical benefit to treatment, understanding patterns of progressive disease (PD) may help differentiate important disease phenotypes in mCRPC. The aim of our study was to evaluate the differences in anatomic sites of PD in patients with pretreatment visceral or bone metastases on time to progression (TTP). Methods: A retrospective review of anonymized patients enrolled in phase 2 and 3 clinical trials was performed. Patients were excluded if lacked Tc bone scan or CT chest, abdomen and pelvis (CT CAP) at baseline. Bone disease was defined by automated bone scan lesion area (BSLA) criteria. All CT CAPs per clinical trial protocol were assessed by RECIST 1.1. Soft tissue PD was noted as target, non-target lesion growth and/or presence of new lesions by anatomic site. Bone PD was defined by > 20% increase in BSLA score. Results: Of the 169 subjects that met our selection criterion, visceral disease was present at baseline in 90 patients (53%). Baseline BSLA score was 90474 mm² in visceral and 80348 mm² in non-visceral patients (p = 0.395). Disease progression occurred in 93 patients (55%). With baseline visceral disease, PD was a result of BSLA in 26 (51%) and visceral disease only in 11 (22%) of patient. Lacking visceral disease at baseline resulted in PD by BSLA in 26 (62%) and visceral disease only in 3 (7%) of patients. There was no significant difference in PFS for baseline visceral/non-visceral involvement; median PFS = 4.5 months in visceral; median PFS = 4.34 months in non-visceral (HR = 1.28; p = 0.244). Conclusions: Patients with visceral disease may still derive a similar clinical benefit from treatment to those without. While the presence of baseline visceral disease was associated with higher rates of PD by visceral involvement, PD by bone disease remained the most common cause of PD regardless of presence of baseline visceral metastases.
Clinically relevant genomic alterations identified by targeted exome sequencing in U.S. veterans with prostate cancer.
Authors: Dadashian Eman , Nakazawa Michael , Parikh Neil Rohit , Kalpage Nathisha , Nickols Nicholas George , Rettig Matthew 
Published: May 2020

e17599 Background: Amongst male United States Veterans, prostate cancer accounts for one third of cancer diagnoses and is the second leading cause of cancer death. Prostate cancers in the Veteran population may have differing frequencies of clinically relevant genomic alterations than the general population owing to chemical exposures, military service, or other unknown factors. Veterans, however, have been underrepresented in large-scale prostate cancer sequencing cohorts to date. Methods: Archival or fresh prostate cancer tissue from Veterans cared for by our team within the VA Greater Los Angeles Healthcare System (a VA Prostate Cancer Center of Excellence) undergo targeted sequencing as part of routine clinical care through the VA Precision Oncology Program. Sequencing covers over 181 genes frequently mutated in cancers. Prostate cancers from 81 Veterans (76 primary tumors, 5 metastases) have been sequenced through the Personalis ACE CancerPlus platform. Results: 43% of Veterans had primary tumors with clinically relevant genomic alterations, including 6.2% with activating mutations in MAPK pathway members (KRAS, ERBB2, or BRAF), 3.7% with somatic mutations in DDR genes (BRCA2 or ATR), 7.3% with mutations in TP53 or RB1, 4.9% in APC, 1.2% in the WNT pathway (CTNNB1), 3.7% with mutations in the PI3K/AKT pathway (PIK3R1 or AKT1), 3.7% with PTEN deletions, and 22.2% had alterations involving an AR regulated gene (SLC45A3 or TMPRSS). Of the five metastatic tumors sequenced, one had a mutation in TP53 and another had an ETS gene fusion detected. Half of the Veterans who underwent tumor sequencing consented for screening for, or enrollment on, active clinical trials at VA Greater LA. Conclusions: Large-scale sequencing of prostate cancers within VA is feasible and may facilitate enrollment in precision oncology trials specifically designed for Veterans. These data suggest that clinically relevant genomic alterations within the primary tumors may differ between Veterans and the general population; larger data sets along with more robust sequencing platforms are required for clarification.
MR guided high intensity focused ultrasound (MRgFUS) for the treatment of oligometastatic prostate cancer bone metastasis.
Authors: Napoli Alessandro , Marchetti Luca , Cortesi Enrico , Marchetti Paolo 
Published: May 2020

e17600 Background: With improvements in diagnostic modalities such as functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Our aim was to determine MRgFUS ability to downstage patients with oligometastatic bone disease with single session of non-invasive metastasis-directed therapy. Methods: The study was designed with intention-to-treat metastatic bone lesions. Patients were enrolled if they had accessible bone metastasis and could safely undergo MRgFUS (InSightec, Israel). Baseline measurable characteristics included dynamic contrast enhanced MRI study (DCE; Gd-BOPTA, Bracco; GE 750 3T magnet) with semiquantitative perfusion analysis, PSA level (ng/ml) and choline PET (SUV). Measurable variables were obtained at treatment time, 3 months, 12 months and 24 months follow-up. Results: 18 patients fulfilled the inclusion criteria and safely underwent MRgFUS procedure of metastatic bone ablations. Lesions were located in the pelvis (11), scapula (3) and long bones (4). At baseline all lesions showed a significant DCE perfusion (highly vascular) with mean perfusion reduction of 88% at 3 months follow-up (CI: 100-50; p < 0.001) stable at subsequent follow-up scans. Similarly PSA levels decreased from a mean baseline of 19 (ng/ml) to 7.1, 2.9 and 2.1, at 3-12 and 24 moths respectively. SUV values showed similar trend with reduction from baseline (mean 8.9 to 3.0, 2.3 and 1.7: p < 0.001). In all patients single MRgFUS session was appropriate without any major or minor adverse events reported. Conclusions: MRgFUS is a totally non-invasive procedure that can obtain complete bone ablation in patients with oligometastatic prostate disease. The technique features a radiation-free approach that can be of incremental value in long-survivor subset on oncological patients, significantly reducing risk of toxic effects. Concurrent chemo regimen is not a contraindication.
Is prostate brachytherapy a dying art? Evidence of increasing utilization in Ontario, Canada.
Authors: Corkum Mark Thomas , Morton Gerard , Louie Alexander V. , Bauman Glenn , Mendez Lucas , D'Souza David , Dinniwell Robert Edward , Velker Vikram M. , Warner Andrew , Rodrigues George 
Published: May 2020

e17608 Background: A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Methods: Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumour-, and provider-factors on treatment utilization over time. Results: 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 ( p< 0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p < 0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 ( p< 0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p< 0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p< 0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p< 0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p< 0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p< 0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Conclusions: Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.
Expansion of germline genetic testing criteria for prostate cancer yields findings across all stages of disease.
Authors: Nielsen Sarah M. , Szmulewitz Russell Zelig , Yang Shan , Truty Rebecca , Michalski Scott T. , Das Kingshuk , Ngo Nhu , Pineda Alvarez Daniel Esteban , Lincoln Stephen E , Nussbaum Robert Luke , Esplin Edward D. 
Published: May 2020

e17615 Background: Increasing evidence suggests criteria for germline testing of patients with prostate cancer (PCa) may miss potentially actionable pathogenic variants. A sponsored testing program with significantly broader criteria was initiated to increase access. Methods: We analyzed de-identified data from 2,252 men with PCa who received at least an 84 gene panel. Inclusion criteria were clinical stage ≥T2 and willingness of the patient and physician to participate. Positive results were categorized as: pathogenic (P), likely pathogenic (LP), or increased risk alleles (IRAs). Results: Clinical stage was available in 1825 men (81%): 541 (30%) were stage II, 228 (12%) stage III, and 1,056 (58%) stage IV (Demographics Table). Among all men, 297 (13%) had positive results, including 286 P/LP variants in 38 genes and 31 IRAs in APC and HOXB13. There was no statistically significant association between stage and positive rate. Of men with positive variants, only 30% reported a family history of prostate, breast, ovarian or pancreatic cancer. The most common positive variants were in BRCA1 (9) , BRCA2 (43) , PALB2 (11) , ATM (36) , CHEK2 (58) , HOXB13 (20) , and mismatch repair genes (8). With respect to ethnicity, the highest positive rate was observed in Ashkenazi Jews (23.8%) and the lowest in African Americans (5.4%). Overall, 190 (70%) of men had P/LP variants conferring eligibility for gene-specific precision therapies or clinical trials based on variants in homologous repair (182), or mismatch repair (8) genes. Conclusions: In a broad PCa patient population, we found overall germline positive rate of 13%, with no statistical difference in this rate with respect to stage. Overall, these data suggest that broader testing criteria and more access to testing could lead to better informed care for many additional patients and their families. [Table: see text]
Retrospective analysis of clinical characteristics and prognostic factors of neuroendocrine carcinoma of the gynecologic tract: A preliminary report of ten years follow-up.
Authors: Zhang Y , Yang J , Li Qy , Zhang Zg , Sun MJ , Shi Yg 
Published: May 2020

e18001 Background: To investigate the clinical characteristics and prognostic factors of neuroendocrine carcinoma of the gynecologic tract (NECGT). Methods: Patients with NECGT diagnosed during 2010 to 2019 were enrolled in this retrospective study. Clinical parameters were calculated, including age, childbearing history, initial symptoms, blood indexs, International Federation of Gynaecology and Obstetrics (FIGO) stages, treatment modalities and survival data. The cut-off values of parameters were screened by receiver-operating characteristic (ROC) curves and their significance was assessed by multivariate logistic regression. Results: We indentified forty five NECGT patients available with the median follow-up time of 5.5 months (9.7±1.98 months). 42 cases (93.3%) originated from cervix uteri, 2 cases (4.4%) from vagina and 1 case (2.2%) from fallopian tube. Irregular vaginal bleeding was the most frequent symptom at the first visit accounting for 75.6%. FIGO stages I to IV distributions were 16 (35.6%), 15 (33.3%), 6 (13.3%), and 8 patients (17.8%). Squamous carcinoma (16.7%) and adenocarcinoma (11.9%) were the common mixed pathological types. 66.7% patients underwent radical surgery, almost all of which received 4-6 cycles adjuvant chemotherapy and half followed by radiation therapy. While data analysis showed that adjuvant radiotherapy could not bring additional survival benefits (p = 0.523). The median PFS of enrolled patients was 14 months (1-78months). Pelvic recurrence (66.7%) and lymphatic metastasis (52.6%) were the main failure patterns. In multivariate analysis, leukocyte count (HR = 0.068, 95%CI: 0.007-0.673, p = 0.021), neutrophil-to-leukocyte ratio (HR = 0.151, 95%CI: 0.024-0.95, p = 0.044), lactic dehydrogenase (LDH) (HR = 6.632, 95%CI: 1.31-33.569, p = 0.022) and carbohydrate antigen-ca 125 (CA-125) (HR = 7.173, 95%CI: 1.25-41.06, p = 0.027) were the independent prognostic factors of PFS. In addition, age at natural menopause (ANM) later than 51.5years (p = 0.009) and an optimal maximum diameter > 62.1mm (p = 0.002) were closely related with poor survival. Conclusions: NECGT is a rare malignant tumor of female genital system. Surgery combined with chemotherapy is the essential treatment, addition of adjuvant radiotherapy did not improve survival. More high-quality clinical trials are needed to provide powerful evidence.
The efficacy and safety of pembrolizumab in advanced cervical cancer—A real world treatment study in an irish healthcare setting.
Authors: Browne Iseult , Fennelly David William , Crown John , Murray Hazel 
Published: May 2020

e18007 Background: Pembrolizumab is a monoclonal antibody that binds to the PD1 receptor blocking its interaction with PDL1 and PDL2, releasing PD1 pathway-mediated inhibition of the immune response. Pembrolizumab is not currently licensed for use in cervical cancer anywhere in Europe. Pembrolizumab was granted approval by the FDA in 2018 for treatment of patients with recurrent or metastatic cervical cancer with progression on or after chemotherapy whose tumours express PDL1 CPS ≥1, based on the interim results from Keynote 158. This showed an ORR of 14.6% in PDL1+ population. The aim of this project was to assess our experience with pembrolizumab in patients with advanced cervical cancer in an Irish Healthcare Setting. Methods: Patients with advanced cervical cancer treated with pembrolizumab at 3 hospitals in Ireland were included. Patients’ clinical data was collected from hard copy and electronic medical records. All patients had recurrent or metastatic cervical cancer. Patients received Pembrolizumab 200mg IV once every three weeks. To enable us to compare our results with the reported outcomes from Keynote 158 we analysed PFS, OS and ORR. Results: Data collection was between April 2018 and December 2019. Patient baseline characteristics include: median age 41 (27-77yrs), 95% FIGO stage IVB, 5% stage IIIB. Histology: 70% SCC, 20% adenocarcinoma, 5% mixed large/small cell, 5% unknown. PDL1 status: 50% positive, 30% unknown, 20% negative. 90% had received previous systemic treatment in the metastatic setting. The ORR was 25% with a DCR of 30%. All responses were in patients with PDL1+ or of unknown PDL1 status. mOS was 8.9months in total population (11.2months in PDL1+), and mPFS was 6.4months (8.3months in PDL1+). 45% of patients experienced all grade toxicity with 10% experiencing grade 3-4. At the time of our analysis 70% had discontinued treatment and 65% of patients had died. Conclusions: The observed activity in our patient population is superior to the interim results from Keynote 158. There are limited therapeutic options in these symptomatic and often terminally ill patients. Additionally all of these alternate treatments create a significant toxicity profile impacting hugely on the patients’ quality of life. Therefore, in our real life experience, pembrolizumab provides an effective and much improved toxicity profile alternative in this patient population. We believe, based on our findings, pembrolizumab should be considered as a standard option for those with advanced PDL1+ cervical cancer.