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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 359-359
    Abstract: 359 Background: The advent of ICIs has dramatically changed the treatment paradigm in mRCC. Although CN was demonstrated to improve survival in combination with cytokine-based therapies, its role is not well-defined in the ICI era. We aimed to compare survival outcomes of patients treated with ICIs, based on their CN status. Methods: The National Cancer Database was queried to identify all patients older than 18 years with mRCC who received ICIs from 2015 to 2018. Chi-Square and Mann-Whitney U tests were used to compare frequency distributions. Cox proportional hazards regression was employed for multivariate analysis of factors associated with overall survival (OS). Results: A total of 4,369 patients were identified- 36.4% (n=1589) had undergone CN. Among patients who got CN, 85.3% were treated with upfront surgery while 13.8% received prior systemic therapy ( P = 0.001). The study population was predominantly Caucasian (89.2%) and male (70.6%). Patients who underwent CN were younger (median age 61 vs. 65 years, P = 〈 0.001). Large primary tumors and clinically node-negative status were associated with higher odds of CN (T4 disease - odds ratio (OR) for 1.49, 95% CI 1.13-3.44, P = 0.03; cN0 disease - OR 1.56, 95% CI 1.23-4.56, P = 0.04). OS after 1 year was significantly higher in patients who underwent CN (66.8% vs 33.2%. P 〈 0.001). On multivariate analysis, CN was independently predictive of improved OS with a hazard ratio (HR) of 0.53 and 95% CI 0.41-0.68, P 〈 0.001. Conclusions: In this large retrospective analysis, CN was associated with improved OS among patients with mRCC receiving ICI-based therapies. Our findings suggest that despite recent advances in systemic therapies for mRCC, CN retains an important role in carefully selected patients.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3447-3447
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3447-3447
    Abstract: Introduction:In this retrospective medical records-based study we analyzed the association between abnormal spontaneous or procedure-related bleeding and patterns of abnormality in tests of platelet function. Commonly used platelet function tests include Platelet Function Analyzer -100 Closure Times (PFA-100 CT), platelet aggregation testing using Light Transmission Aggregometry (LTA), and platelet dense granule release assay (by lumi-aggregometry). Other related tests include Von Willebrand factor (VWF) analysis, platelet flow-cytometry for cell surface glycoprotein expression, and electron microscopy. LTA in our center uses five different agonists - ADP, arachidonic acid, collagen, epinephrine and ristocetin, while lumi-aggregometry is performed using four agonists - ADP, arachidonic acid, collagen and epinephrine. Methods:This study included 497 patients who had platelet aggregation testing done using LTA between August 2008 and August 2013. Sixty-nine percent (n = 354) of these patients had a history of abnormal bleeding. Since the data were not normally distributed, Wilcoxon rank-sum test (for continuous variables) and Fisher's exact test (for categorical variables) were used wherever appropriate. P value of 〈 0.05 was considered as significant. Results:Of the patients with a history of abnormal bleeding, 81% had spontaneous bleeding, 29% had surgery/procedure-related bleeding, and 13% had history of both types of abnormal bleeding. Three hundred nine of these patients had a recent ( 〈 4 weeks) bleeding event. Abnormal bleeding, recent or historical, was found to associate significantly with impaired platelet aggregation, as well as platelet release in response to ADP, arachidonic acid, collagen or epinephrine (P 〈 0.001 for all). Abnormal aggregation and release in response to ≥2 different agonists was also significantly associated with abnormal bleeding, as was the total number of abnormalities on the aggregation and release panel (P 〈 0.001). A history of a recent bleeding event ( 〈 4 weeks) was found to be associated with reduced aggregation in response to arachidonic acid (P = 0.001), impaired aggregation and release in response to collagen (P =0.04 and 〈 0.001 respectively), and reduced platelet release in response to epinephrine (P = 0.005). Recent bleeding also correlated with the total number of abnormalities in the aggregation (P = 0.002) and release panels (p =0.03). No significant association was found between a history of abnormal bleeding (either recent or historical) and prolonged PFA-100 closure times (collagen/ADP or collagen/epinephrine), or any abnormality in VWF analyses or platelet flow-cytometry studies. Conclusions:While PFA-100 closure times, VWF analyses and platelet flow-cytometry panel failed to show an association with abnormal bleeding (historical or recent), impaired platelet aggregation or release in response to several agonists was found to correlate with abnormal spontaneous and/or procedure-related bleeding, recent as well as historical, suggesting that platelet aggregation and release assays may be useful in diagnosis of a bleeding diathesis in patients with an appropriate clinical history Disclosures McCrae: Halozyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syntimmune: Consultancy; Momenta: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4634-4634
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4634-4634
    Abstract: Introduction: With the expanding repertoire of antiplatelet drug targets and therapies, quantifiable parameters to assess their efficacy can prove to be useful in clinical decision-making. In this retrospective analysis we examined patients who had platelet aggregation testing done at our center between August 2008 and August 2013, focusing on those who were on some form of antiplatelet therapy during testing. Our goal was to define the impact of platelet aggregation testing on decision-making regarding continuation or change in antiplatelet therapy. Methods: Light transmission aggregometry (LTA) was used to assess efficacy of treatment with antiplatelet agents. Inhibition of platelet aggregation in response to ADP and arachidonic acid are reflective of the therapeutic effect of aspirin, while inhibition of platelet aggregation in response to ADP reflects the effect of P2Y12 receptor antagonists. As per parameters developed at our center, the combination of arachidonic acid aggregation 〈 20 percent and ADP aggregation (at concentration of 5 uM) 〈 70 percent is indicative of optimal therapeutic response to aspirin. Though not fully standardized, ADP aggregation 〈 40% is considered to be indicative of therapeutic response to clopidogrel. Descriptive statistics for frequency were used. Pearson coefficient was used to assess correlation. Results: We studied results of platelet aggregometry in 117 patients who were on some form of antiplatelet therapy - 81 on a single agent (72 on aspirin alone, 9 receiving P2Y12 antagonist alone), 34 on dual therapy (33 on aspirin + P2Y12 antagonist, 1 on aspirin + cilostazol), and 2 patients on triple therapy (1 on aspirin + P2Y12 antagonist + cilostazol, 1 on aspirin + dipyridamole + cilostazol). None of our patients were on Gp IIb/IIIa inhibitors. In total, 108 patients were on aspirin therapy and 43 patients were on P2Y12 inhibitors. In 65 out of these 117 patients, the primary indication for platelet aggregation testing was to monitor the efficacy of antiplatelet therapy, while in the remaining 52, testing was done for other indications. Fifty-nine of these 65 patients were tested in the setting of a recent thrombotic event in the cerebral, coronary, peripheral, or other vascular bed. While 68 (58%) patients had optimal therapeutic response, 49 (42%) patients - 38 of the 108 (35%) patients on aspirin, and 14 of the 43 (32%) patients on a P2Y12 inhibitor - had evidence of suboptimal response to the respective agent. However, antiplatelet therapy was changed or adjusted in only 8 of these 49 patients following these sub-optimal test results, and only 3 had repeat testing following the change (all three of whom were shown to have complete response). Among the 108 patients on aspirin therapy, the total daily dose did not correlate either with the PFA-100 closure times (Collagen/ADP or Collagen/epinephrine) or with the degree of platelet aggregation in response to any of the agonists (ADP, arachidonic acid, collagen, epinephrine or ristocetin). Conclusions: Most of the patients who underwent platelet aggregation testing to monitor the efficacy of antiplatelet therapy had a recent thrombotic event that prompted the test. Though 42% of patients on antiplatelet agent(s) had in vitro evidence of sub-optimal platelet inhibition, antiplatelet therapy was changed or adjusted in only 16% of these individuals, and only 6% had repeat testing following the change. This suggests that, though platelet aggregation testing was potentially useful in monitoring efficacy of platelet inhibition, clinical changes in antiplatelet therapy were guided more by other factors, casting uncertainty upon the cost effectiveness of platelet function testing in this population. No significant increment was found in the in vitro antiplatelet effect of aspirin with increasing daily doses, suggesting lack of a dose-response beyond 81 mg per day. Disclosures McCrae: Syntimmune: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Halozyme: Membership on an entity's Board of Directors or advisory committees; Momenta: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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    detail.hit.zdb_id: 80069-7
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 113-113
    Abstract: 113 Background: The prognosis of refractory mCRPC remains poor despite advancements in therapeutic options. KeyNote-199 demonstrated modest activity of Pem in mCRPC with expected safety profile. We present our real-world experience with Pem in mCRPC. Methods: We conducted a retrospective review of mCRPC patients treated with Pem at our institution from 1/1/2017 to 10/1/22. Baseline demographic, clinicopathologic, and genomic characteristics were recorded. PSA and radiographic responses were assessed by the study team, and survival distributions estimated using the Kaplan-Meier method. Results: A total of 39 patients were identified – 97% (37) were White, median age was 71 years, 4% (19/35) had a Gleason Score ≥8; 80% (31) had skeletal and 74% (29) had soft tissue metastases at Pem initiation. Overall, patients were heavily pre-treated (median of 7 prior therapies, range 0-8) - 87% (34) had received taxanes, 82% (32) novel antiandrogens, 23% (9) Ra-223, 21% (8) Sipuleucel-T, and 2% (1) Olaparib. Median duration on Pem was 7 months (range = 1-29). Among the 34 evaluable patients, 2 (6%) achieved CR, 2 (6%) had PR, 5 (15%) had stable disease (SD), and 25 (73%) had progressive disease (PD) on radiographic assessment. PSA reduction ≥ 50% was noted in 7/32 (22%) patients. The 4 patients who had radiographic CR/PR had positive predictive biomarkers – Patient 1: CR – MSI-H, high TMB (17.5/Mb); Patient 2: CR – MSI-indeterminate, germline MSH6 mutation; Patient 3: PR – MSI-H, high TMB (28.8/Mb), germline MSH2 mutation; and Patient 4: PR – MSI-S, high TMB (18.3/Mb), PDL1 TPS 100%, positive neuroendocrine markers. Interestingly, patient 3 was switched to ipilimumab + nivolumab after PD on Pem, and subsequently had a CR. None of the evaluated patients with SD or PD had high MSI, TMB, or PDL1 levels. The median overall survival from Pem initiation was 4.4 months (95% CI 3.0-10.2 months). Three (8%) patients discontinued Pem due to immune-related adverse effects (IRAEs); no treatment-related deaths were reported. The most frequent Gr 3 IRAEs are shown. Conclusions: Single-agent Pem demonstrated modest overall efficacy in mCRPC, restricted only to patients with predictive biomarkers. Given the non-trivial risk of IRAEs, financial toxicity, and potential QoL implications, we suggest using checkpoint inhibitors only in appropriately biomarker-selected patients with mCRPC. [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: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. TPS406-TPS406
    Abstract: TPS406 Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). Neoadjuvant androgen ablation has not improved high-risk pathological features or recurrence rates after RP. 1 We reported the association between high intratumoral CD8 + T lymphocyte (CTL) density and improved survival post-RP, suggesting clinical benefit from neoadjuvant immunomodulation (NI). 2 Analysis of the tumor immune microenvironment after NI may also provide key insights into potential therapeutic strategies in PCa. CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9 and CXCL10) are downregulated while MDSC/Treg-attracting chemokines (CCL2, CCL22, and CXCL12) are upregulated in human PCa tissue. 3 A large proportion of T cells in PCa are Tregs or dysfunctional CTLs and this immunosuppressive profile may be partly driven by COX-2 upregulation. 4,5 A chemokine modulating regimen (CKM) of rintatolimod (TLR-3 ligand), aspirin (COX-2 inhibitor), and IFN-α favorably reprogrammed the chemokine profile and CTL/Treg ratio in human PCa explants. 3 This combination has demonstrated safety in phase I/II trials across other tumor types, though it is unclear if IFN-α can be omitted without compromising efficacy. 7-8 Methods: This is a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP are randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (rintatolimod + aspirin + IFN-α) vs CKM doublet (rintatolimod + aspirin) vs no CKM. Thirty patients will be enrolled to assess CD8 + T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations will be secondary endpoints. Pre- and post-treatment density of various infiltrating T cell subtypes, MDSCs, chemokine and chemokine receptor profiles, immune checkpoint expression, immune-regulatory gene expression signatures, and peripheral blood immune cell landscape will be key exploratory endpoints. The trial is currently open with 11 patients enrolled. Clinical trial ID: NCT03899987 . References: 1) Scolieri MJ, J Urol 2000, 2) Clin Oncol 36, 2018: suppl; abstr 5068, 3) Muthuswamy R, Prostate 2016, 4) Sfanos KS, Prostate 2009, 5) Gupta S, Prostate 2000, 6) NCT01545141, 7) NCT02151448, 8) NCT02432378.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: The Lancet, Elsevier BV, Vol. 390, No. 10100 ( 2017-09), p. 1151-1210
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 472-472
    Abstract: 472 Background: Timely initiation of NAC is critical to improve outcomes in MIBC. Medicaid expansion through the Affordable Care Act improved racial disparities in healthcare access for patients with advanced cancers. This study aimed to assess the association of Medicaid expansion with racial disparities in time-to-NAC in MIBC. Methods: This case-control study queried the National Cancer Database for 18-64 years old Black and White adults who were diagnosed with stage II & III bladder cancer and treated with NAC from Jan 1, 2008 to Dec 31, 2018. The primary endpoint was the timely receipt of NAC, defined as initiation within 45 days from the diagnosis of resectable MIBC. Racial disparity was defined as percentage-point (PP) difference for Black vs. White patients, adjusted for age, sex, income level, clinical stage, and year of diagnosis. Results: The study included 5053 patients (7.2% Black, n = 391). In states without Medicaid expansion, Black patients became less likely to receive timely NAC than their White counterparts (2008-2013: Black 59.6% vs White 63.8%, p = 0.53; 2014-2018: Black 47.9% vs White 61.2%, p 〈 0.01). In contrast, the racial disparity was narrowed in states with Medicaid expansion (2008-2013: Black 35.7% vs White 62.9%, p 〈 0.01; 2014-2018: Black 53.4% vs White 59.5%, adjusted PP difference -2.4; p = 0.20). The adjusted difference-in-differences estimate revealed a 26.0 PP reduction in racial disparity (95% CI, 8.1%-44.0%; p 〈 0.01). Conclusions: Medicaid expansion was associated with significant reduction in racial disparity between Black and White patients in the timely receipt of NAC for MIBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 343-343
    Abstract: 343 Background: The population of prostate cancer (PCa) survivors has grown over the recent decades, with many reporting long-term treatment-related physical, emotional, and financial adverse effects resulting in greater psychological distress compared to males without a history of PCa. This study analyzes the prevalence of psychological distress among PCa survivors and its impact on emergency room (ER) utilization and overall survival. Methods: We identified a cohort of 3,453 PCa survivors from the 2000-2018 National Health Interview Survey (NHIS) linked to the National Death Index Mortality Files through Dec 31, 2019. Deaths that occurred during the first two years of follow-up were excluded from analyses to minimize the likelihood of reverse causation. The Kessler Psychological Distress Scale (K6) was used to quantify psychological distress. Severe, moderate, and none/low mental distress have been validated for thresholds K6≥13, 13 〉 K6 ≥5, and 5 〉 K6 ≥0. Its association with self-reported ER utilization during the 12 months preceding the survey and all-cause mortality was estimated using weighted multivariable logistic regression and Cox proportional hazards regression, respectively. Models were adjusted for age, sex, race, educational attainment, comorbidities, region, year of survey, smoking status, health insurance, functional limitations, and time since cancer diagnosis. Results: Among the 3,453 PCa survivors (mean [SD] age 68.5 [7.2] years; 2479 (77.9%] non-Hispanic White, 655 (14.1%) non-Hispanic Black; median time since cancer diagnosis:5 years), 435 (11.3%) and 96 (2.4%) reported moderate and severe psychological distress respectively. PCa survivors with psychological distress tend to be younger, less educated, single, and with multiple comorbid conditions, and functional limitations. 812(22.8%) of PCa survivors visited the ER during 12 months preceding the survey. During a median follow-up of 81 months, 937(25.5%) of survivors died of all causes. After adjusting for covariates, PCa survivors with severe psychological distress were at a higher risk of ER utilization and all-cause mortality than those with moderate or no distress. Conclusions: Psychological distress was associated with increased risk of ER utilization and all-cause mortality among PCa survivors. Greater efforts are needed to understand, recognize, and alleviate such distress, as well as to enhance social and mental/physical health support in this rapidly growing community of vulnerable cancer survivors. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 4540-4540
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 4537-4537
    Abstract: 4537 Background: Recent use of immune checkpoint inhibitors (CI) has improved overall survival (OS) in a subset of patients (pts) with metastatic UC. Intra-patient tumoral heterogeneity and epithelial-to-mesenchymal transition has been hypothesized as a driver of treatment resistance to both chemotherapy and CI in UC. There is a critical need to evaluate heterogeneity in UC for biomarkers of treatment response and new therapeutic targets. Trop2 is hypothesized to play a role in UC progression and is the target of a new antibody-drug conjugate, IMMU-132 that is being tested in UC trials. We report the phenotypic comparison of PDL1 expression among CTC subpopulations in UC pts. Methods: Peripheral blood samples were collected from pts with UC treated at Cleveland Clinic and U. of Wisconsin. Immunomagnetic capture and CTC enumeration using both EpCAM and Trop2 from matched blood samples was performed in the VERSA platform. Protein expression for PDL1 in these CTC populations was quantified. Longitudinal analysis of UC pts treated with chemotherapy or CI is ongoing. Results: CTC were captured using EpCAM and Trop2 in all 10 pts in our initial cohort. The frequency of Trop2 CTC was higher than EpCAM CTC with a mean of 248 Trop2 CTC (range 2-1885) compared to 76 EpCAM CTC (range 1-632). PDL1 expression was more frequent in Trop2 CTC than EpCAM CTC. In two pts progressing on Atezolizumab, Trop2 CTC had a higher frequency of PDL1 expression compared to EpCAM CTC (85% vs 2% in pt 1 and 2% vs 0% in pt 2). In pts followed longitudinally, Trop2 CTC dropped from 1885 to 1 in a pt with response to Atezolizumab and PDL1+ CTC declined from 4 to 0. After 1 cycle of Carbo/Gem in another pt, EpCAM CTC declined from 46 to 3 while Trop2 CTC from 116 to 47. Conclusions: This is the first report of CTC heterogeneity in pts with UC identifying high frequency of Trop2 CTCs with variable expression of PDL1 across different pts. Early results from longitudinal analysis suggest CTC as potential predictive / pharmacodynamic biomarkers of treatment response. Prospective data validation in larger cohort is ongoing, while IMMU-132 clinical trials in UC may provide context for future validation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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