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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 309-309
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 309-309
    Abstract: 309 Background: High prostate specific antigen (PSA) at diagnosis is associated with worse outcomes in patients (pt) with prostate cancer. However, treatment selection and clinical outcome in those diagnosed with an extremely high PSA ( 〉 500 ng/ml) are not well characterized, and we aim to better study this unique pt population. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer pts seen between 2010-2018, we identified 23 pts with a PSA 〉 500 at prostate cancer diagnosis. Descriptive analysis was performed to capture clinical characteristics, treatment selection and response, and outcomes in this cohort. Results: The median age and PSA at diagnosis were 64 (54-85) and 1057 ng/ml (528-11,418). At presentation, 1 pt had localized versus 22 pts had metastatic disease, 3 were asymptomatic, and sites of metastasis included lymph nodes (LN) only (n=3), bone only (n=8), or LNs and bone (n=11). Pts were initiated on either first line androgen deprivation (ADT) or ADT plus docetaxel if seen after 2015 (1 refused). All pts had 〉 90% PSA response to first line therapy, with median PSA nadir 4.38 ng/ml (0.06-153), duration of response 6 months (1-33), and time to castration-resistant prostate cancer (CRPC) 14.5 months (5-99). There are differences in treatment selection and outcomes for pts treated with ADT vs. ADT plus docetaxel first line (see table). Conclusions: In pts with PSA 〉 500 at prostate cancer diagnosis, we have observed significant heterogeneity in clinical presentation and response to treatment. In pts treated with first line ADT plus docetaxel, we observed 2 of 7 pts with extended treatment response ( 〉 42 months). Differences in disease biology may account for this observation, and molecular characterization will be needed to better understand this subset. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 117-117
    Abstract: 117 Background: Prostate cancer (PCa) and especially advanced PCa largely affects older adults with a median age of diagnosis of 67. Despite ART’s role as a mainstay of treatment (tx) in advanced PCa, little is known about its risks/benefits in older adults. We aimed to examine survival outcomes and safety in patients (pts) with mCRPC ≥75 years-old (y.o) on ART. Methods: The records of mCRPC pts treated with ART at the Mount Sinai Hospital between 2010 and 2021 were screened for demographics, medical history, ART course, tx toxicity, and survival outcomes. PSA progression free survival (PFS) between pts ≥75 y.o and pts ≤75 y.o was assessed as the primary outcome. Secondary outcomes were overall survival (os) and tx toxicity. Tx toxicity was evaluated using physician documented tx side-effects (SE)s. Fischer’s exact was used to compare baseline characteristics and tx SEs. Cox proportional hazards models were used to compare survival outcomes. Results: Of 153 pts, 97 were 〈 75 y.o and 56 were ≥75 y.o. Within the 〈 75 y.o group, 17 (17.5%) were post-chemo compared to 7 (12.5%) in the ≥75 group (p = .493) Relevant baseline characteristics (ECOG ≥2, Race, Gleason 4-5, hospitalizations, and CCI) were not significantly different. Median PSA PFS was 14.2 (≥75 y.o) and 17.3 months ( 〈 75 y.o) with no significant difference on univariate or multivariate analysis (HR: 1.1 [0.69, 1.74;] p = 0.697. Median OS was 32.4 months for the ≥75 y.o cohort and 32.3 months for the 〈 75 y.o cohort (HR: 1.38 [0.88, 2.17;] p = 0.156). The 5 most common SEs by group are reported below. Of note, adults ≥75 y.o were more likely to report edema compared to the 〈 75 y.o pts (8.2% vs 21.4%, p-value = .026). Conclusions: Pts ≥75 on ART experienced similar survival benefits compared with pts 〈 75. While older adults were more likely to report edema, overall tx toxicity profiles did not differ significantly. Ultimately, these findings ground evidence-based counseling and tx for older adults with mCRPC considering ART. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17575-e17575
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17575-e17575
    Abstract: e17575 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients received treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 1/2020, 38 of 40 planned men with mCRPC were enrolled, 28 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 54+ weeks, median time to PSA progression after therapy completion is 14.7+ weeks (95%CI; 5.5-23.9+ weeks). PSA response rates showed successive improvements with each sequential treatment module (Table). Eight patients (21.1%) continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (82+ weeks, 79+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (15.8%), diarrhea (5.3%), anemia (2.6%), fatigue (2.6%), neutropenia (2.6%), and thrombocytopenia (2.6%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17047-e17047
    Abstract: e17047 Background: The addition of docetaxel or a novel hormonal agent (NHA), such as abiraterone acetate or enzalutamide, has become standard of care for mHSPC, but prospective data for comparative efficacy remains limited. Clinical variables abstracted through natural language processing of free text from patient charts can provide real-world data to answer important clinical questions. Methods: Using an innovative data abstraction process, we retrospectively identified men with de novo mHSPC within deidentified charts from the Mount Sinai Health System treated with either docetaxel or a NHA between January 1, 2014 and April 30, 2019. Dates were chosen to reflect the timeline for which these therapeutic agents received regulatory approval for mHSPC, but also to allow sufficient clinical follow up after treatment initiation. Primary outcome of failure-free survival (FFS), defined as the time to next treatment, was assessed using the Kaplan-Meier method and multivariable Cox proportional hazards models. We additionally performed multivariable analysis to evaluate the prognostic significance of post-treatment PSA nadir on FFS. Results: A total of 94 de novo mHSPC patients that received either docetaxel or an NHA were identified using proprietary Sema4 data abstraction process: 52 received docetaxel, 42 received an NHA. Use of an upfront NHA in mHSPC was associated with a significantly longer FFS compared to docetaxel (20.7 vs. 10.1 months, p = 0.023). While NHAs were associated with a significantly longer FFS than docetaxel in patients with high metastatic burden of disease (25.12 vs. 9.63 months, p = 0.014), this was not observed in low-volume disease (20.71 vs. 26.5 months, p = 0.9). In multivariable model analysis adjusting for age, baseline PSA, and metastasis burden, docetaxel remains independently associated with worse FFS compared to NHA (HR 1.96, 95% CI 1.12−3.45, p = 0.019). Irrespective of docetaxel or NHA use, lower post-treatment PSA nadir levels were associated with improved FFS (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, 〉 0.4ng/ml, respectively; p 〈 0.001). Conclusions: Clinical variables abstracted from deidentified clinical documentation can efficiently provide relevant and reliable data upon which clinical research can be based. Comparative analysis of real-world data demonstrates superior FFS in de novo mHSPC treated with a NHA as compared to docetaxel. The depth of PSA response holds prognostic value for mHSPC outcomes, regardless of treatment used.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 166-166
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 166-166
    Abstract: 166 Background: Prostate cancer is a heterogeneous disease with differences in tumor stromal interactions contributing to variability in treatment response and outcome. Gene expression of peripheral blood cells is altered by interactions with neoplastic tissue. We previously developed a peripheral whole blood six-gene signature prognostic for survival in mCRPC. Here we evaluate how different clinical disease states and treatment with different therapeutic agents impact this signature. Methods: Whole blood was collected in PAXgene Blood RNA tubes in two cohorts of prostate cancer patients, one at Mount Sinai (n=135), the other in Munich (n=59), in the context of prospective clinical studies. Whole blood RNA was extracted and the six target genes were amplified using qPCR. Scores were derived using normalized cycle threshold (ΔCT) values of the six genes, according to the model: 2 x ABL2 + SEMA4D + ITGAL – C1QA – TIMP1 – CDKN1A. Patients were categorized by disease state in the Mount Sinai cohort, and by treatment received in the Munich cohort, for data analysis. Results: CRPC is the only disease state with a mean six-gene score (18.06) above the high-risk cutoff (17.9), and is significantly higher than localized or hormone sensitive advanced disease (16.07, 16.52, respectively; p=0.0002). Among patients with localized disease, there was no significant difference in the mean six-gene scores for patients with low-, intermediate-, and high-risk disease (16.07, 15.33, 16.66, respectively; p=0.27). In CRPC patients treated with docetaxel, there are significant changes to the six-gene score over the course of treatment (p=0.002), with a notable percentage decrease (-6.2%) at the 2-8 week timepoint that is not observed in patients treated with abiraterone or enzalutamide. Conclusions: Gene expression profiling of whole blood is influenced by the clinical state of prostate cancer as seen by differences to the six-gene score from localized to castrate resistant disease. Cytotoxic chemotherapy appears to modulate the six-gene score, something not seen with AR-directed therapies. Further investigation will be needed to understand the significance of these changes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 563-563
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 563-563
    Abstract: 563 Background: Advances in diagnostic and treatment modalities have resulted in better outcomes in metastatic renal cell carcinoma (mRCC) patients. With new therapies extending survival, we hypothesize that pattern of metastatic disease has evolved over time. We assessed the pattern of metastases as reported in baseline characteristics of prospective clinical trial patients between 1990 and 2018. Methods: This study identified all phase I-III mRCC therapeutic clinical trials published between January 1990 and July 2018 in PubMed and ClinicalTrials.gov. Studies that included patients with other cancers or did not report metastases were excluded. Data was stratified to examine differences in three listed treatment eras for first-line therapy. Linear regression models were used to evaluate temporal trends and subcategorized as either First Line Only treatments (FLO) or Second-Line and Beyond (SLB). Results: 127 clinical trials encompassing 16534 subjects were identified. Between 1990 and 2018, rates of lymph node metastases in the FLO population increased significantly at 1.03% per year ( P 〈 0.05). The rate of lung and liver metastases in FLO showed a trend of increase at 0.48% and 0.04% per year, respectively, but decreased -0.73% and -0.15% per year in the SLB population. Moreover, rate of bone metastasis showed a trend of increase in both populations, particularly between the VEGF/TKI and Immunotherapy/TKI eras in the SLB population (18.89% to 29.19%). Conclusions: Notable changes were found in the pattern of metastasis in patients with mRCC. Increasing rate of bone metastasis may warrant dedicated bone imaging for routine staging in patients with mRCC. These evolving patterns may have important implications in treatment selection and prognosis in this patient population. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 89-89
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 89-89
    Abstract: 89 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay/prevent drug resistance, and minimize toxicity. Methods: Enrolled patients all received 3 consecutive treatment modules, each 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 10/2019, 35 of 40 planned men with mCRPC were enrolled, 25 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 52 weeks, median time to PSA progression after therapy completion is 15.5 weeks (95%CI; 5-26.1+ weeks). PSA response rates show successive improvements with each sequential treatment module (Table). Six (24%) patients continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (64+ weeks, 54+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (14.3%), diarrhea (5.7%), anemia (2.9%), fatigue (2.9%), neutropenia (2.9%), and thrombocytopenia (2.9%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 184-184
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 184-184
    Abstract: 184 Background: Prostate Specific Antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer (PC). Currently, the significance of PSA at death is undefined. In this single institution retrospective study, we aim to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we stratified patients into the following cohorts based on their PSA at death: 〈 10, 10-100, 100-1000, and 〉 1000 ng/ml. We excluded data of patients who had less than 3 visits to the Mount Sinai Hospital. A descriptive analysis was performed to assess clinical characteristics of disease, treatment response, and outcomes. Results: We identified 1097 PC patients, and 101 were found to be deceased following a diagnosis of mCRPC. Cohorts of higher PSA level at death were associated with: a lower Gleason score at diagnosis, a longer time to castration resistance, higher burden of metastatic disease at death (non-visceral and visceral), and longer OS in patients with mCRPC (see table). Conclusions: In this study, PSA at death is associated with several important clinical characteristics and outcome, including overall survival. These differences may be attributed to their underlying biologic behavior. These results are hypothesis generating, and larger studies will be needed to further assess the significance of these findings. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 170-170
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 170-170
    Abstract: 170 Background: While satraplatin, a fourth generation oral platinum analogue, failed to improve overall survival (OS) in an unselected metastatic castrate-resistant prostate cancer (mCRPC) population (Sternberg, JCO 2009), anti-tumor activity was demonstrated, suggesting a “platinum-sensitive” subset of patients. Predictive biomarkers may not only select patients most likely to benefit from novel “targeted” therapies but also from standard (even discarded) cytotoxic agents. Development of predictive biomarkers in mCRPC is hampered by the fact that PC is associated with a long natural history and evolving genetic changes, highlighting the need for immediate pre-treatment metastatic tissue samples for biomarker development. In this trial, we sought to determine the feasibility of obtaining metastatic biopsies in patients with mCRPC treated with satraplatin. Methods: Docetaxel-refractory mCRPC patients underwent image-guided biopsy of metastatic lesions prior to treatment with satraplatin 80 mg/m 2 PO on days 1 to 5 of a 35-day cycle and prednisone 5 mg PO twice daily. Biopsy samples are analyzed by whole exome and RNA sequencing, and peripheral blood samples are undergoing transcriptional profiling, to facilitate biomarker development. Results: Thirteen patients were enrolled with a median age of 71 (range: 55 to 80), prostate-specific antigen (PSA) of 82 ng/ml (0.04-3057), and Gleason score 8 (7 to 9). All patients received prior docetaxel, four (31%) had more than or eqaul to two prior chemotherapies, and two (15%) received abiraterone. Drug-related grade 3/4 toxicities included leukopenia (23%), neutropenia (8%), thrombocytopenia (8%), fatigue (8%), renal failure (8%), dysphagia (17%), and diarrhea (8%). A median of four cycles of satraplatin were completed, with declines of serum PSA of greater than or equal to 30% achieved in 4 of 13 patients (31%; 95% CI, 57.3 to 85.4%). Median time to PSA progression was 12.4 weeks (95% CI, 7.2 to 29.7+ weeks). Metastatic pre-treatment biopsies were collected in all study patients; genomic analysis is ongoing. Conclusions: This study confirms that satraplatin has anti-cancer activity in a subset of patients with mCRPC. Trials that require pre-treatment metastatic tumor biopsies are feasible. Analysis of the correlation between molecular signatures and treatment response will be presented at the meeting. Clinical trial information: NCT01289067.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e17022-e17022
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17022-e17022
    Abstract: e17022 Background: The prevalence of testicular cancer in adolescents and young adults creates a unique opportunity for education through social media. We investigated this populations’ baseline knowledge of testicular cancer (TC) and testicular self-examination (TSE) and identified the efficacy of various forms of media in educating young individuals. Methods: A survey was designed to assess participants’ baseline knowledge of TC and TSE. Participants were randomly shown one of three forms of educational media created by the Testicular Cancer Society and the National Cancer Institute. These were an infographic, a short (60 second) and a long (6 minute) video. Participants were then asked to correctly identify facts regarding TC and TSE. Baseline knowledge was analyzed by age ( 〈 24 vs. 〉 25), and post-media knowledge was analyzed to determine the efficacy of each media form. Results: Responses from 328 participants were analyzed, with a mean age of 24.3 years, 40.9% male, 72.0% white, and 70.7% graduated college or a graduate program. Only 30.7% of participants reported being educated about TC, 25.9% correctly identified the 15-35 age group as having the highest prevalence of TC, and 26.3% correctly identified the TC survival rate as being 75-100%. The 〉 25-year-old group were significantly more likely to have heard of TSE (p 〈 0.001), performed a TSE if male (p = 0.043), encouraged males to perform TSE if female (p 〈 0.001) and correctly identify TC survival rate (p = 0.006) and treatability (p = 0.007). Long video viewers were significantly less likely to watch it in its entirety compared to infographic and short video viewers, and they were less likely to report an understanding of TSE compared to infographic viewers. Short video viewers were less likely to have properly identified the TC survival rate compared to both infographic (P 〈 0.001) and long video viewers (p = 0.001). Conclusions: Overall there is poor awareness and education regarding TC and TSE, with adolescents performing significantly worse than young adults. The infographic performed the best overall in completion and education about TC and TSE, with the short video performing similarly well, and the long video performing the worst. This suggests that easily dispersed and viewable forms of media may be the most effective tool for educating young people.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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