bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of anti-prostate-specific membrane antigen (PSMA) antibody J591 for men with metastatic castration-resistant prostate cancer (mCRPC) and unfavorable circulating tumor cell (CTC) count.
Authors: Lebenthal Justin M , Sun Michael , Nauseef Jones T. , Niaz Muhammad Junaid , Imad Dunya , Christos Paul J. , Fernandez Escarleth , Singh Sharon , Chamberlain Tessa A , Osborne Joseph , Babich John , Molina Ana M. , Sternberg Cora N. , Nanus David M. , Bander Neil Harrison , Tagawa Scott T. 
Published: March 2021

120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA targeted radionuclide therapy has been associated with decline in CTC count, but it remains unclear whether this effect results from radionuclide-induced cytotoxicity. J591 was engineered to have antibody-dependent cytotoxicity. A subset of patients was observed to have CTC count decline following imaging with 111In-J591, so a prospective study was launched to test the hypothesis that “naked” J591 leads to CTC count decline. Methods: In a Simon 2-stage dose de-escalation study, men with progressive mCRPC and unfavorable CTC count (CellSearch > 4) received a single dose of J591. Initial dose cohort 300 mg with de-escalation to 20 mg. CTC count was re-assessed 4, 8, and 12 weeks following therapy along with PSA and standard imaging. An optional PSMA PET was included prior to treatment. The primary endpoint was proportion of subjects with conversion to favorable CTC count ( < 5 CTCs/7.5 mL blood) and/or > 30% decline from baseline within 12 weeks post-treatment. Results: 10 men were enrolled, 9 of whom were evaluable (1 died of progressive mCRPC prior to post-treatment CTC count). Median age was 71.5 years (range 60-81), 78% had prior chemo, ECOG PS 1 in 45% and 2 in 55%. 7 of 9 (78%) evaluable subjects were Halabi CALGB prognostic poor risk category and 2 (22%) intermediate. 6 of 9 had pre-treatment PSMA PET/CT (three 89Zr-J591 and three 68Ga-PSMA11). Though not required, all scans showed > 1 lesion with SUVmax > liver SUV (range 9.12-70.15). 2 of 6 in the 300 mg cohort had CTC count decline; 1 of 6 converted to favorable count (9 to 0 with decrease of 35 to 12 in other). 3 were treated with 20 mg; 1 had CTC count decline of 316 to 112, but 0 converted to favorable count. Across both cohorts, 3 of 9 had a CTC count decline at any point in time, ranging from 65-100% decline. With the pre-specified 2-stage design, enrollment was halted for futility based upon the primary endpoint of 12-week CTC count. PSA values post-treatment increased in 8 (89%) patients and remained unchanged in 1 (11%) patient. Conclusions: Single-agent anti-PSMA antibody J591 may lead to decline in CTC count, though the study did not meet its primary endpoint. A combination or maintenance approach might be preferable and is worthy of exploration.
Baseline and post-treatment circulating tumor cell (CTC) counts with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sun Michael , Lebenthal Justin M , Nauseef Jones T. , Niaz Muhammad Junaid , Guervil Sabrina , Fernandez Escarleth , Patel Amie , Tan Angela , Vlachostergios Panagiotis J. , Osborne Joseph , Molina Ana M. , Sternberg Cora N. , Nanus David M. , Bander Neil Harrison , Tagawa Scott T. 
Published: March 2021

158 Background: CTC counts are an independent prognostic factor in men with mCRPC; certain changes following treatment (conversion from detectable to undetectable or unfavorable to favorable) are associated with improved overall survival. Most PSMA-TRT efficacy data have focused on PSA or imaging changes. Here, we describe baseline and post-treatment CTC counts from subjects receiving PSMA-TRT. Methods: Men with mCRPC treated on prospective clinical trials of PSMA-TRT and with available CTC counts (CellSearch) were included in our analysis. Depending upon the era of the trial, post-treatment counts were performed at 4-6 (initial era) or 12 weeks (recent era) after a single cycle of PSMA-TRT (individual trial data reported elsewhere). We describe CTC counts at baseline and compare pre-treatment counts to those after PSMA-TRT. Results: 116 men treated with PSMA-TRT had baseline CTC count (90 with both pre- and post-treatment CTC). Forty-four patients (37.9%) received 177Lu-J951, 46 (39.7%) received 177Lu-PSMA-617, and 26 (22.4%) received 225Ac-J591. Median age was 71.5. Fifty-eight patients (50%) had previously received taxane chemotherapy, median PSA was 82.98 ng/mL, and 66 (56.9%) were in the high-risk Halabi (CALGB) prognostic group. Eighty-nine out of one hundred sixteen (76.7%) had detectable baseline CTC and 58/116 (50%) had unfavorable baseline CTC count. Forty-nine out of seventy (70%) had post-treatment CTC count decline, 23/70 (32.9%) converted from detectable to undetectable, and 17/47 (36.2%) converted from unfavorable to favorable. CTC changes stratified by type of PSMA-TRT are reported in the table. Conclusions: This is the largest analysis of CTC changes in patients who have received PSMA-TRT. In addition to PSA changes and other previously reported outcomes, even when low doses of radionuclide therapy as part of dose-escalation studies are included, the majority with detectable CTC counts have post-treatment CTC count decline. A significant portion of patients experience favorable CTC changes. [Table: see text]
CTC counts as a biomarker of prognosis and response in metastatic castration-resistant prostate cancer (mCRPC) from the CARD trial.
Authors: De Bono Johann S. , Pantel Klaus , Efstathiou Eleni , Sternberg Cora N. , Castellano Daniel , Fizazi Karim , Tombal Bertrand , Wulfing Christian , Schonhoft Joseph D. , Gill Audrey , Chu Lincy , Wenstrup Rick , Ozatilgan Ayse , Geffriaud-Ricouard Christine , Macé Sandrine , De Wit Ronald 
Published: March 2021

161 Background: In the prospective CARD trial (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer who had received docetaxel and progressed within 12 months with the alternative androgen-signaling-targeted inhibitor. Here we analyzed circulating tumor cell (CTC) counts as a biomarker of prognosis and response to therapy. Methods: Blood samples collected at screening (SC), Cycle 2 (C2) Day 1, and end of therapy were sent to Epic Sciences for CTC analysis. The association between CTC counts, defined as any cytokeratin-positive, CD45-negative cell, and clinical outcomes were pre-specified and analyzed using a multivariate Cox model for time-to-events (rPFS, OS) or a Χ2 test for categorical outcomes (objective tumor response). Results: Of the 255 patients randomized, 237 (92.9%) had evaluable samples at SC and 213 (83.5%) at C2. CTCs ≥ 1 were detected in 204 samples at SC (86%) and 178 samples at C2 (84%), with a median (interquartile range) count per mL of blood of 4.1 (1.3–14.2) and 5.2 (1.5–17.3), respectively. At baseline, higher CTC counts were associated with higher values of lactate dehydrogenase (P = 0.014), alkaline phosphatase (P < 0.001), and prostate-specific antigen (P < 0.001). High CTC counts, measured as a continuous variable at SC (all arms combined) were associated with a shorter OS (P = 0.03), but not rPFS (P = 0.7). However, favorable changes in absolute CTC count from SC to C2, all arms combined, were associated with longer rPFS (P = 0.03). Conversion from high (≥ 3) to low (< 3) CTC count at C2 or maintenance of a low CTC count at C2 was associated with objective tumor response (P = 0.007). Analysis of the associations of CTC androgen receptor variant 7, chromosomal instability, heterogeneity status (Shannon Index), single-cell genotypes (e.g. retinoblastoma/phosphatase and tensin homolog copy-loss), and the presence of CTCs with small-cell/neuroendocrine morphology is ongoing. Conclusions: This preplanned analysis of the CARD trial confirms that baseline CTC counts, measured by Epic Sciences platform, are prognostic. Moreover, early favorable changes in CTC counts from baseline to C2 are associated with response to therapy. Funding: Sanofi. Clinical trial information: NCT02485691.
Implementation of clinician-facing prostate cancer therapeutic clinical trial decision tool at a comprehensive cancer center.
Authors: Borno Hala , Li Patricia , Zhang Sylvia , Idossa Dame , Desai Arpita , Rodvelt Tammy J. , Bose Rohit , Koshkin Vadim S , Chou Jonathon , Friedlander Terence W. , Huang Franklin W. , Small Eric Jay , Aggarwal Rahul Raj 
Published: March 2021

19 Background: The conventional model for clinical trial (CT) recruitment relies on clinicians to identify potential CTs for patients. Internet technology can be leveraged as a decision tool to enhance the CT recruitment process. Methods: An internet-based, clinician-facing decision tool was developed in genitourinary medical oncology clinic at a Comprehensive Cancer Center (CCC). The tool provided access to a real-time, tailored list of treatment CTs actively recruiting patients with PCa at the CCC based on clinical characteristics inputted by user. The clinical data was summarized. All clinicians (n = 9) with access to the decision tool completed a survey to assess effectiveness and satisfaction. Results: During a 9-month pilot period, user engagement increased from a baseline of 36 to 136 cases per month, with a total of 644 cases overall. Among cases, 525 had metastatic disease, 436 of which were metastatic castration resistant PCa (mCRPC). Overall, 145 cases were classified as having oligo-metastatic ( < = 3) PCa, 93 of whom were also mCRPC. Prior treatments received included abiraterone in hormone-sensitive PCa (HSPC 19.3%, CRPC 48.7%); enzalutamide (HSPC 3.7%, CRPC 34.9%) apalutamide (HSPC 1.3%, CRPC 6.9%), taxane (HSPC 17.2%, CRPC 27.8%), radium-223 (6.1%), sipuleucel-T (18.3%), parp inhibitors (4%), or check-point inhibitors (6%). Clinician-inputted genomics of cases included CDK12 (20.9%), MSI-high disease (13.6%), BRCA1/2 (32.7%), ARID1a (7.3%), ATM (21.8%), FANCA (4.5%), or CHEK2 (6.4%) and HDAC2 (0.9%). Among survey respondents, use of tool in clinic was reported sometimes (22%), often/always (78%). Results of decision tool were reported to inform treatment sometimes (22%) or often/always (78%). Respondents confidence in often/always knowing all available CTs increased from a baseline of 0% to 89%, and 89% of users reported very/complete satisfaction with decision tool. Conclusions: An internet-based CT decision tool for provides detailed clinical characteristics of patients for whom CTs are being considered at a CCC. Clinicians using the decision tool report high levels of satisfaction. The tool was effective in increasing confidence in knowledge of current available CTs. Data gathered in the decision tool may inform future CT development. Future research with expanded use of decision tool among referring clinicians will assess its impact in promoting diversity among CT participants.
Factors influencing noncompletion of radiotherapy among men with localized prostate cancer.
Authors: Dee Edward Christopher , Muralidhar Vinayak , Arega Melaku A , Kishan Amar Upadhyaya , Spratt Daniel Eidelberg , Dess Robert Timothy , King Martin T. , Sha Sybil , Santos Patricia Mae G , Butler Santino , Sanford Nina Niu , Nguyen Paul L. , Mahal Brandon Arvin Virgil 
Published: March 2021

199 Background: Treatment non-completion may occur with radiotherapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment non-completion and RT fractionation schedules. Methods: The National Cancer Database identified men diagnosed from 2004-2014 treated with primary RT. Patients receiving 180cGy/fraction (conventional), 200cGy/fraction (conventional), 250cGy/fraction (moderate hypofractionation), and 300cGy/fraction (moderate hypofractionation) were defined as having completed radiotherapy if they received ≥40 fractions, ≥37 fractions, ≥28 fractions, and ≥19 fractions, respectively. Stereotactic body radiotherapy (SBRT) was defined as 5-8 fractions of 600-800cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for various sociodemographic covariates. Propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival. Results: Of 93,079 patients, 90.5% (N = 84,260) received conventional fractionation, 2.3% (N = 2,181) received moderate hypofractionation, and 7.1% (N = 6,638) received SBRT. Rates of non-completion were 10.0% (N = 8,406) among patients who received conventional fractionation, 7.5% (N = 163) among patients who received moderate hypofractionation, and 1.7% (N = 115) among patients who received SBRT (OR versus conventional: 0.214, 95%CI 0.177-0.258, P < 0.001). The rate of non-completion among 15,417 African American patients was 11.8%, compared to 8.8% among 74,189 white patients (OR 1.39, 95%CI 1.31-1.47, P < 0.001). On subgroup analysis, the disparity in non-completion persisted for conventional fractionation (12.4% vs. 9.4%, OR 1.36, 95%CI 1.29-1.44, P < 0.001) and moderate hypofractionation (13.6% vs. 6.6%, OR 2.24, 95%CI 1.52-3.29, P < 0.001), but not for SBRT (2.0% vs. 1.6%, OR 1.25, 95%CI 0.76-2.06, P = 0.384). Non-completion was associated with worse survival on propensity-adjusted multivariate analysis (HR 1.37, 95%CI 1.31-1.43, P < 0.001). Conclusions: SBRT was associated with lower rates of RT non-completion among men with localized prostate cancer. African American race was associated with greater rates of treatment non-completion, although the disparity may be decreased among men receiving SBRT.
Myocardial perfusion PET imaging to evaluate coronary microvascular dysfunction in men with prostate cancer receiving androgen deprivation therapy.
Authors: Narayan Vivek , Guerraty Marie , Demissei Biniyam G , Haas Naomi B. , Takvorian Samuel U , Parikh Ravi Bharat , Vaughn David J. , Pryma Daniel A. , Mankoff David A. , Ky Bonnie 
Published: March 2021

211 Background: Strategies to inform cardiovascular (CV) risk are needed for prostate cancer patients initiating androgen deprivation therapy (ADT). Reduced myocardial blood flow reserve (MBFR) and coronary microvascular dysfunction (CMD) represent functional counterparts of traditional CV risk factors, including hyperlipidemia, insulin-resistance, and the metabolic syndrome. Myocardial perfusion PET stress imaging quantifies MBFR and detects CMD. However, the potential utility of these measures to indicate adverse CV changes in prostate cancer patients receiving ADT is poorly understood. Methods: In this prospective study (NCT03535987), eligible prostate cancer patients were planned for at least 6 months of ADT and curative-intent radiation therapy. All patients had a Framingham 10-year general CV risk score of at least 10% and no prior ADT exposure. Myocardial perfusion PET stress imaging was performed within 3 weeks of ADT initiation and again following 6 months of ADT exposure. MBFR was calculated as the ratio of MBF during stress / MBF during rest, and CMD was defined per established criteria as reduced MBFR (ratio < 2.0) in patients without coronary artery disease. Study outcomes included the change in MBFR following 6 months of ADT exposure and the incidence of reduced MBFR and CMD. McNemar’s test and Wilcoxon signed rank test were used for comparison of paired data. Results: Fifteen patients completed baseline myocardial perfusion PET imaging, of whom 13 completed follow-up imaging at 6 months. At baseline, the median (IQR) Framingham CV risk score was 30.4% (19.6, 35.5). One patient (7.7%) had reduced MBFR at baseline, and 5 additional patients (46.2%) developed newly reduced MBFR (ratio < 2.0) within 6 months of ADT initiation (p = 0.025). While no patients had CMD at baseline, 3 patients (30%) developed incident CMD (p = 0.083). MBFR declined in 69% of patients [median decline -0.32 (IQR -0.51, -0.22)] over 6 months ADT exposure. Conclusions: Myocardial perfusion PET imaging demonstrated a high incidence of reduced MBFR and CMD within 6 months of ADT initiation. These findings support further investigation of myocardial PET imaging, a widely-available clinical tool, as a potential research and clinical strategy to inform CV risk assessment in prostate cancer patients receiving ADT. Clinical trial information: NCT03535987.
Financial toxicity and patient-provider communication about cancer-related cost among prostate cancer patients and survivors.
Authors: Kranzler Elissa C. , Miller Melissa F. , Fortune Erica E. , Geynisman Daniel M. , Bohannon Linda S. , Badt Heather , Zaleta Alexandra Katherine 
Published: March 2021

215 Background: With early screening and advances in treatment, prostate cancer (PC) patients are living longer and facing increasingly complex therapeutic decisions alongside significant financial burden related to care (e.g., copays, coinsurance, other out-of-pocket (OOP) costs). Conversations with providers about financial concerns can help patients navigate these decisions, thereby promoting delivery of quality care and improving quality of life. We characterized financial toxicity (FT) and patient-provider communication about cancer-related cost among PC patients and survivors. Methods: 107 PC patients and survivors enrolled in Cancer Support Community’s Cancer Experience Registry completed items assessing FT (11-item FACIT-COST measure; range = 0-44, lower scores indicate greater FT). Items include ability to meet monthly expenses, financial stress, and cancer/treatment influence on financial situation. Frequencies and correlations between FT, health care team (HCT) communication, and socio-demographics were examined. Results: Participants were 89% non-Hispanic White, 5% Black, 2% Hispanic; mean age was 68 years (SD = 7.5). Median time since diagnosis was 3 years; 19% reported experiencing symptoms of PC at the time of diagnosis. 21% were ever metastatic, 22% experienced a recurrence, and 48% reported currently receiving treatment. 29% were employed full- or part-time; 52% spent at least $100/month on all OOP PC costs, 30% spent $250 or more, 16% spent $500 or more. Mean FT score was 28 (SD = 11.9). 67% reported members of their HCT did not discuss cost of treatment, 55% did not discuss impact of PC and treatment on work, 77% did not discuss financial distress. While most participants were satisfied with their doctor’s explanation of benefits (89%) and risks/side effects (79%) for each treatment option, only 49% were satisfied with how much their HCT discussed financial costs of each option. Greater patient confidence in communicating with doctor about PC was significantly associated with less FT ( r= .19, p< .05), but experiencing more FT was not correlated with a greater likelihood of HCT discussing cost of treatment ( r= -.05, p= .63) or discussing impact of cancer and treatment on work ( r= .04, p= .67). Conclusions: Results indicate that patients with greater financial toxicity report less confidence in communicating with their doctor about PC, however providers are not frequently or systematically initiating discussions around cost and impact on work even among those experiencing the highest levels of financial burden. Findings underscore the critical value of transparency about health care costs and impact, as well as support for providers in communicating effectively with patients about costs and available resources, to improve patient quality of life and health outcomes.
Visual analogue scales (VAS) as exploratory evaluation of eight dimensions in prostate cancer (PCa) patients aged 60 years and older initiating a gonadotropin-releasing hormone agonist (GnRHa) therapy: Secondary analysis of PRISME study.
Authors: Hennequin Christophe , Mongiat-Artus Pierre , Roupret Morgan , Pello Leprince Ringuet Nathalie , Grandoulier Anne-Sophie , Rozet Francois 
Published: March 2021

221 Background: Age, PCa and GnRHa treatment may modify patients health-related quality of life (HRQOL) and clinical parameters routinely evaluated: health status, urinary function, sexual function, memory, mood, motricity, autonomy. Our purpose was to investigate the use of VAS in these 8 domains before and after a 6-month GnRHa therapy, in order to simplify questions and minimize administration burden in future routine practice. Methods: Between March 2018 and February 2020, a prospective, multicenter, non-interventional study was conducted in France (PRISME, NCT03516110). Urologists, radiation oncologists and medical oncologists recruited patients aged 60 years and older, with histologically confirmed PCa, initiating a GnRHa therapy. 1000 patients were planned to be included 1:2:1 in prespecified age groups ([60-70[, [70-75[, ≥ 75 years). They reported their levels of satisfaction in the 8 domains at baseline and after a 6-month GnRHa treatment. Each item included a title and a 10 cm-linear analogue scale with descriptive phrases anchored at the ends (0: not satisfied at all; 10: totally satisfied). Significant changes were concluded in case of means 95% CIs not including 0. Correlations between VAS and validated questionnaires on the same dimensions changes were evaluated through Pearson correlation. Results: The final analysis included 652 patients (full analysis set population), enrolled by 138 investigators. Mean (±SD) age was 72.5±6.2 years. 71.6% had at least one comorbidity at baseline and 65.0% were receiving at least one concomitant systemic treatment. Main reasons for GnRHa initiation were high risk in 65.3%, metastatic stage in 18.4%, biochemical recurrence in 13.3%. 36% had received at least one prior treatment for PCa (prostatectomy 57%, radiotherapy 34.5%). Respectively, 47.1%, 58.0% and 17.6% presented at least one urinary symptom, one sexual symptom, or one other clinical symptom at baseline. Baseline mean [CI 95%] scores were: 7.5 [7.3-7.6] in general QOL, 6.8 [6.6-7.0] in general health status, 6.2 [6.0-6.4] in urinary function, 3.4 [3.2-3.6] in sexual function, 7.0 [6.8-7.2] in mood, 7.0 [6.9-7.2] in memory, 7.6 [7.4-7.8] in motricity and 8.0 [7.9-8.2] in autonomy VAS. At follow-up, significant and clinically relevant overall change was observed in sexual (-1.2 [-1.4;-0.9]) VAS. No correlations were found between the changes in VAS and in validated questionnaires. Conclusions: The exploratory use of VAS in the 8 dimensions routinely evaluated in elderly PCa patients treated with GnRHa therapy showed interesting results. No correlations could be shown between evolution in VAS and in validated questionnaire scores. Further explorations on this topic remain to be made. Clinical trial information: NCT03516110.