GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    HERCULES: A prostate cancer (PC) sequencing panel for parallel analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 5036-5036
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5036-5036
    Abstract: 5036 Background: In metastatic PC, tracking genomic alterations over time and with treatment can predict disease outcomes, guide treatment, and identify novel therapeutic targets. Analysis of peripheral blood ctDNA offers a non-invasive liquid biopsy for genomic profiling, but ctDNA often comprises a small portion of total cell-free DNA (cfDNA) in the blood, requiring high depth of sequencing which may still miss PC-relevant variants. We and others have shown that single CTCs captured from the same blood sample yield additional PC-relevant genomic data when combined with ctDNA profiling, but currently there is no assay that can be applied uniformly to both analytes. Here, we present a new amplicon-based sequencing panel capable of detecting PC-relevant variants in both cfDNA and single CTCs. Methods: PC-relevant genes were curated by overlapping reviews of cBioPortal for cancer genomics, the catalogue of somatic mutations in cancer (COSMIC), and PC-relevant genomic literature. HERCULES targets 36 genes with 258 amplicons covering PC-associated mutations and copy number variations. AmpliSeq HD targeted sequencing technology was applied for analysis of both cfDNA and CTCs. Analytical validation was performed sequentially, first using AcroMetrix and Seracare DNA control samples, then single and pooled LNCap and PC3 PC cells and cfDNA, then 8 patient peripheral blood samples of matched plasma cfDNA and single CTCs captured using the RareCyte platform from participants in SWOG S1802, an ongoing CTEP/CIRB-approved phase 3 trial for men with metastatic PC. Results: In DNA control samples with allele frequencies of 1%, 0.25%, and 0.1%, HERCULES displayed sensitivity of 100%, 75%, and 50%, respectively. In matched single cells and cfDNA from cell lines, HERCULES detected 100% of database-annotated somatic variants in cfDNA and in pools of 2 or more cells, and it identified 〉 90% of variants in single cells. In 16 matched patient samples of cfDNA and single CTCs, with read coverage depths of 〉 50,000x for 20ng cfDNA and 〉 1,500x for single CTCs, HERCULES detected shared variants (mean N per sample = 6.1) as well as unique somatic variants (mean of 1.1 CTC variants not called in the cfDNA, and 4.1 cfDNA variants not called in the CTCs). Conclusions: HERCULES is, to our knowledge, the first PC-specific targeted sequencing panel capable of parallel genomic profiling of both ctDNA and CTCs. In our preliminary analytical validation, it detected somatic variants with high sensitivity in matched cfDNA and CTC samples. With additional validation, HERCULES has the potential to augment conventional ctDNA profiling by illuminating both cell-free and cellular genomic evolution during PC treatment and progression.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.5036
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Evaluation of basal and luminal subtypes of urothelial carcinoma in African American and non-African American patients.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 305-305
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 305-305
    Abstract: 305 Background: African American (AA) patients with urothelial carcinoma (UC) have been known to have a worse prognosis even when corrected for variables such as tumor stage and grade. Analysis of gene expression of several malignancies has resulted in the discovery of molecular subtypes with well-defined intrinsic biology. Recent studies in high grade (HG), muscle-invasive UC have led to the identification of two intrinsic, molecular subsets termed “luminal” and “basal” with characteristics of stages of urothelial differentiation, and that remarkably reflect the luminal and basal-like molecular subtypes of breast cancer. Patients with basal-like UC have a significantly worse overall survival. Methods: A total of 215 HG muscle-invasive UC tumors from the MDACC (n=75) and TCGA (n=140) were used to make intrinsic subtype calls using gene expression profiling (MDACC: DASL [cDNA-mediated Annealing, Selection, extension, and Ligation] and TCGA: RNA seq). Basal and luminal subtype calls were derived using previously published subtype classifiers (Damrauer et. al. PNAS, 2014 and Choi et. al. Cancer Cell, 2014). Patients were classified into AA and non-AA (white, Hispanic, or Asian) based upon self-reported race. Results: In total there were 16 and 199 tumors from AA and non-AA patients respectively. In non-AA patients, the proportion of tumors that were classified as basal and luminal were approximately equal (93 and 106 respectively), while in AA patients, there was enrichment of basal tumors (12 basal and 4 luminal) (p=0.03735, Fisher’s exact test). Conclusions: AA patients are enriched in the basal molecular subtype of UC. Similar findings have been previously documented in AA women with breast cancer. The enrichment of basal UC in AAs suggests that a biological explanation may in part underlie the poor outcomes seen in AA patients. Future studies will explore the prognostic and predictive implications of basal subtype in AA patients with UC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.7_suppl.305
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    A phase II trial of risk-adapted treatment for muscle invasive bladder cancer after neoadjuvant accelerated MVAC.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. TPS537-TPS537
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. TPS537-TPS537
    Abstract: TPS537 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy (Cx) or chemoradiation (CRT) is the standard of care for urothelial carcinoma (UC) pts with muscle invasive bladder cancer (MIBC). Both Cx and CRT carry potential short and long-term toxicity and quality of life implications. Recent work has shown that mutations in DNA damage repair/response genes are predictive of pathologic downstaging after NAC at the time of Cx, with those pts achieving pT0 disease demonstrating excellent long-term survival (Van Allen et al. Cancer Discov. 2014; Plimack et al. Eur Urol. 2015; Liu et al. JAMA Oncol. 2016; Teo et al. CCR. 2017). Sparing pts Cx or CRT after NAC without compromising oncologic outcomes would improve quality of life and decrease morbidity. Methods: A phase II, parallel arm, multi-institutional clinical trial (NCT02710734) is being conducted to evaluate a risk-adapted approach to treatment of MIBC. Pts with cT2-T3N0M0 UC of the bladder, ECOG PS 0-1 and CrCl≥50 mL/min, undergo NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin. Simultaneously, the pre-NAC TURBT specimen is submitted for deep sequencing to identify variants in a panel of cancer-relevant genes (Caris Life Sciences, Phoenix, AZ). Those with an alteration in ATM, RB1, FANCC or ERCC2 and no clinical evidence of disease by restaging TUR and imaging post-NAC will begin a pre-defined active surveillance regimen that includes urinary cytological, cystoscopic, and radiographic evaluations. The remaining pts will undergo bladder-directed therapy at the discretion of the pt and clinician applying either intravesical therapy ( 〈 cT2 post-NAC), CRT or Cx (≤cT2 post-NAC) or Cx (≥cT3 post-NAC). The primary objective is metastasis-free survival (MFS) at 2 years for all enrolled and evaluable pts. The trial has a non-inferiority design with a 14% margin between risk-adapted treatment (MFS = 78%) and standard-of-care (MFS = 64%) with a sample size of 70 pts, 82% power and a type I error of 0.045. Key secondary and translational objectives: assess the rate of UC recurrence in active surveillance pts; validate biomarkers of response to NAC; evaluate urinary biomarkers consistent with persistent UC. Clinical trial information: NCT02710734.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.6_suppl.TPS537
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Cell-free DNA methylation as a predictive biomarker of response to neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer in SWOG S1314.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 4506-4506
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4506-4506
    Abstract: 4506 Background: Neoadjuvant chemotherapy is the standard of care in muscle-invasive bladder cancer patients. However, treatment is intense, the overall benefit is small, and there is no established marker to identify patients who benefit most. The aim of the study is to characterize cell-free DNA (cfDNA) methylation from patients receiving neoadjuvant chemotherapy in SWOG S1314, a prospective cooperative group trial, and to correlate the methylation signatures with pathologic response. Methods: Blood samples were collected prospectively from 73 patients before and during standard neoadjuvant chemotherapy. At radical cystectomy, pathologic response was documented. Plasma cfDNA was profiled using Infinium MethylationEPIC BeadChip array. Differential methylation between pathologic responders (≤pT1N0M0) and non-responders was analyzed, and a Random Forest model was used to generate a classifier predictive of treatment response. Results: Using pre-chemotherapy plasma cfDNA, we developed a methylation-based response score (mR-score) predictive of pathologic response. The mR-score also could be calculated using plasma samples collected after the first cycle of neoadjuvant chemotherapy, resulting in a similar predictive ability. Furthermore, we used cfDNA methylation data to calculate the circulating bladder DNA fraction, which had a modest but independent predictive ability for treatment response. When we combined the mR-score and circulating bladder DNA fraction, we successfully predicted pathologic response outcomes in 79% of patients based on their plasma collected before chemotherapy and after 1 cycle of chemotherapy. Conclusions: Our study provides proof of concept that cfDNA methylation may be used to predict treatment response in bladder cancer patients receiving neoadjuvant chemotherapy. Clinical trial information: NCT02177695.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.4506
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Baseline circulating tumor cell (CTC) count as a prognostic marker of PSA response and progression in metastatic castrate sensitive prostate cancer (mCSPC): Results from SWOG S1216, a phase III randomized trial of androgen deprivation plus orteronel (cyp17 inhibitor) or bicalutamide.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 5506-5506
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5506-5506
    Abstract: 5506 Background: In mCSPC, androgen deprivation therapy (ADT) combined with chemotherapy or androgen receptor signaling inhibition (ARSI) is the new standard of care. Biomarkers that predict clinical outcomes with these therapies are needed. We hypothesized that CellSearch CTC count, an FDA-cleared biomarker in metastatic castrate resistant PC (mCRPC), may be a valuable biomarker in mCSPC. Methods: In S1216, peripheral blood was drawn with informed consent at registration (baseline), and CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini) per standard manufacturer protocol. CTC counts were analyzed centrally for associations with 2 pre-specified trial intermediate endpoints: 7-month PSA (7mPSA) ≤ 0.2 ng/ml vs. 0.2–4.0 vs. 〉 4.0, (intermediate endpoint for overall survival, OS); and progression-free survival (PFS) 〈 vs. 〉 2 years. Because OS data have not matured, analysis was pooled and equal numbers of samples were analyzed from each treatment arm and outcome measure (7mPSA and PFS) as stipulated by the Data Safety Monitoring Committee. Results: From 2014 to 2017, 523 baseline samples were collected. In the 7mPSA analysis (n = 264), CTCs were detected in 38% of men, with a median of 4 CTCs in those with detectable CTCs. In the PFS analysis (n = 336), CTCs were detected in 37% of men, with a median of 3 CTCs in those with detectable CTCs. Adjusting for disease burden (minimal vs. extensive) and ADT status (already initiated or not) at the time of CTC measurement, men with undetectable CTCs were 6.1-fold more likely to attain 7mPSA ≤ 0.2 (OR 6.1, 95% CI 2.1-17.2, p 〈 0.001) and 3.7-fold more likely to achieve 〉 2 years PFS (OR 3.7, 95% CI 1.7-8.1, p 〈 0.001) compared to men with baseline CTCs ≥ 5. Other cutpoints previously validated in mCRPC studies (CTC 〈 5 vs. ≥5 and CTCs 0 vs. ≥1) also strongly discriminated 7mPSA and PFS with statistical significance in this mCSPC cohort. Conclusions: CTC count at the start of treatment for mCSPC was highly prognostic of 7-month PSA response (intermediate endpoint for OS) and of PFS at 2 years. To our knowledge, this is the first such strong evidence from a prospective phase 3 trial of this magnitude. Additional analyses are planned when the trial is fully reported. Baseline CTC count may serve as a valuable prognostic marker to discriminate men likely to respond favorably to hormonal therapies from those who may benefit from early alternate interventions.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.5506
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Muscle-invasive bladder cancer: Molecular subtypes and response to neoadjuvant chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 6_suppl ( 2017-02-20), p. 281-281
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 281-281
    Abstract: 281 Background: Molecular subtypes of muscle-invasive bladder cancers (MIBC) have recently been discovered based on gene expression. We investigated the impact of different subtyping methods on response to neoadjuvant cisplatin-based chemotherapy (NAC) and developed a single sample model for subtyping. Methods: Transcriptome-wide microarray analysis was conducted on pre-NAC transurethral resection (TUR) specimens of 223 patients with MIBC who received NAC followed by cystectomy at 5 centers. The specimens were classified according to four published methods for molecular subtype (UNC, MDA, TCGA, Lund). Overall survival (OS) for each subtype was compared between NAC patients in this study and non-NAC patients from the provisional TCGA. A genomic classifier (GSC) was trained to predict subtype in a single sample model and validated in independent NAC (2 centers) and non-NAC datasets. Results: The models generated subtype calls similar to previously published ratios. Concordance of a given subtype between the different methods was high. Luminal tumors had the best OS independent of NAC. Patients with tumors classified as UNC basal, MDA basal and TCGA cluster III experienced the greatest improvement in OS after NAC compared to surgery alone. Tumors assigned as UNC claudin-low had the worst OS irrespective of treatment regimen (p=0.005). GSC accurately predicted four classes (luminal, luminal-infiltrated, basal, claudin-low) and the differential impact of a basal subtype on patient OS in NAC (3-yr survival of 75.2%; p=0.001) and non-NAC (3-yr survival of 42.4%; p=0.014) cohorts could be validated. Conclusions: The benefit of NAC varies between molecular subtypes. The good prognosis of luminal/cluster I tumors could not be improved with NAC, which suggests these patients may be managed best with surgery alone. The prognosis of patients with basal tumors improved the most when treated with NAC compared to surgery alone. Poor OS of claudin-low tumors even after NAC implies that these tumors are resistant to cisplatin-based chemotherapy, and these patients should be included in protocols investigating alternative treatment options like immunotherapy. Further validation prior to clinical implementation is needed.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.6_suppl.281
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Baseline circulating tumor cell (CTC) count as a prognostic marker of overall survival (OS) in metastatic hormone sensitive prostate cancer (mHSPC): Results from SWOG S1216, a phase III randomized trial of androgen deprivation plus orteronel (cyp17 inhibitor) or bicalutamide.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 5080-5080
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5080-5080
    Abstract: 5080 Background: Biomarkers are needed to predict clinical outcomes in mHSPC. We previously reported that baseline CTC counts in S1216 were prognostic of PSA response and disease progression ( ASCO 2020; CCR 2021). However, the trial’s primary overall survival (OS) endpoint was not yet mature at that time. Here we present the final results of S1216 using all available samples to assess the prognostic value of CTC counts for response, progression, OS, and treatment arm interactions. Methods: In S1216, peripheral blood was drawn with informed consent at registration (baseline) and at progression to metastatic castrate resistant prostate cancer (mCRPC). CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini). CTC counts were evaluated for associations with 3 pre-specified trial endpoints: 7-month PSA (7mPSA) ≤ 0.2 ng/ml vs. 0.2–4.0 vs. 〉 4.0 using a generalized logit model; and progression-free survival (PFS) and OS using Cox regression. Results: From 2014 to 2021, 503 evaluable samples were collected at baseline and 93 at progression. Baseline CTC count was ≥5 in 11.9% of samples, 1-4 in 19.3%, and 0 in 66.8%. Comparing men with 0 vs. ≥5 CTCs at baseline, those with 0 CTCs were significantly more likely to attain a complete PSA response and had significantly lower risk of a PFS event and death after adjusting for clinical covariates (disease burden, bone metastases, age, race, alkaline phosphatase, hemoglobin, PSA, treatment arm). These associations were not modified by treatment arm. Progression CTCs 〈 5 vs. ≥5 also were prognostic of OS (logrank p=0.001), consistent with prior findings in mCRPC. Same-patient CTC counts in matched baseline-progression pairs (n=61) were highly correlated (Spearman p 〈 0.001). Conclusions: CTC count at the start of treatment for mHSPC was highly prognostic of PSA response, PFS, and OS; associations that held in both treatment arms. Moreover, baseline CTC count strongly correlated with progression count, suggesting that mild vs. aggressive disease phenotypes may persist from mHSPC to mCRPC. This evidence from a large prospective phase 3 trial suggests that baseline CTC count is a valuable prognostic marker in men initiating therapy for mHSPC, discriminating those likely to experience favorable vs. unfavorable response and OS. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.5080
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Atezolizumab with platinum and etoposide chemotherapy followed by cystectomy for patients with localized small cell neuroendocrine bladder cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 6_suppl ( 2023-02-20), p. TPS599-TPS599
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. TPS599-TPS599
    Abstract: TPS599 Background: Small cell bladder cancer (SCBC) is a rare aggressive bladder cancer (BC) variant comprising 〈 1% of BC. Recommended front line etoposide and platinum chemotherapy for SCBC is extrapolated from small cell lung cancer (SCLCA) studies. Data describing small cell bladder cancer treatment are predominantly retrospective. Substitution of etoposide for gemcitabine with cis or carboplatin is widely accepted. This extrapolation is based on histologic similarity between the rare SCBC, and more common SCLCA. Recently, several teams have shown DNA mutation patterns are also more consistent between SCBC and SCLCA, compared to SCBC and urothelial bladder cancers, further supporting the divergence in treatment. These patterns which characterize this “neuronal” subgroup in the TCGA dataset, also reinforce this group has the poorest OS outcome vs other subtypes. Patients with SCBC are nearly uniformly excluded from BC trials, and thus the response to checkpoint inhibition and other novel therapies in SCBC is unknown. As SCBCs often respond to, then quickly recur post chemotherapy, novel active therapies are needed. Immune checkpoint blockade with anti-PD(L)1 antibodies is clinically active, leading to objective responses in approximately 15-25% of patients with urothelial cancer, and 33% in biomarker selected patients with SCLCA. In IMpower133, Atezolizumab + carboplatin + etoposide vs chemotherapy alone demonstrated significant OS advantage (12.3 vs 10.3 months) in frontline ES SCLCA, a practice changing milestone. Like urothelial bladder and SCLCA, we believe SCBC may have dramatic response to checkpoint inhibitors, as shown in small case series from our team and others. Methods: Patients with invasive (cT1-cT4) small cell/neuroendocrine carcinoma of the bladder (MIBC), with or without urothelial cancer component, who are eligible for radical cystectomy and platinum chemotherapy and immunotherapy will be enrolled. Patients with N1 disease within the true pelvis are eligible. Atezolizumab 1200 mg IV Day 1 of every 21 day cycle with etoposide and investigator choice cisplatin or carboplatin chemotherapy x 4 neoadjuvant cycles will be delivered. The primary objective is to assess pathologic complete response rate following protocol therapy. Following cystectomy, Atezolizumab maintenance Q 21 days will continue until unacceptable toxicity or loss of clinical benefit for up to 1 year (e.g., 16 cycles). With type I and type II error rates of 5 and 10% respectively, the first stage will consist of 15 patients. If 6 or fewer patients respond, the study will terminate after the first stage. Otherwise, accrual will continue to 34 patients. If 17 or fewer patients respond at the end of the second stage, the study will terminate after the second stage. If 18 or more patients respond, accrual will continue to 63 patients. Secondary endpoints include rates of DFS and OS. Clinical trial information: NCT05312671 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.6_suppl.TPS599
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Oncologic outcomes in patients with residual invasive upper tract urothelial carcinoma following neoadjuvant chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 6_suppl ( 2023-02-20), p. 475-475
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 475-475
    Abstract: 475 Background: Emerging evidence supports use of neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for appropriately selected patients with upper tract urothelial carcinoma (UTUC). However, oncologic outcomes have not been well characterized for patients with residual muscle-invasive disease after NAC. Methods: We used a multi-institutional cohort from 24 centers in the U.S., Europe, and Japan to retrospectively identify patients who underwent RNU for UTUC from 1985-2022 and had high-grade muscle-invasive disease. We stratified the cohort based on receipt of NAC ( 〉 ypT2 vs. 〉 pT2). Exclusion criteria included receipt of adjuvant chemotherapy, concurrent cystectomy with RNU, and distant metastatic disease. Baseline characteristics were compared between groups. Kaplan-Meier survival analysis with log-rank test was used to compare differences in recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Multivariable Cox regression and Fine-Gray competing risk regression were used to determine predictors of these outcomes. Results: A total of 1,233 patients were included, 62 of whom received NAC prior to RNU. A platinum-based regimen was used in 90% of NAC recipients, and the median number of cycles administered was 4 (IQR: 3-5). Median follow-up time among all patients was 22 months (IQR: 8-47 mo.). NAC recipients were more likely to have pathologic node positivity (35% vs. 13%) and less likely to have positive tumor margins (8% vs. 28%). On Kaplan-Meier analysis, NAC recipients with residual 〉 ypT2 disease had poorer outcomes than those with 〉 pT2 disease (2-year RFS [NAC vs. no NAC]: 52% vs. 80%, p 〈 0.001; 2-year OS: 60% vs. 78%, p=0.003; 2-year CSS: 61% vs. 86%, p 〈 0.001). Multivariable analyses also showed a statistically significant association between residual muscle-invasive disease after NAC and poorer RFS, OS, and CSS (Table). Conclusions: NAC recipients with 〉 ypT2 disease at RNU after exhibit poorer outcomes than stage-matched chemotherapy naïve counterparts. This may reflect effects of occult micrometastatic disease or chemoresistant primary tumors in non-responders. Our data highlight the need to improve prospective identification of candidates most likely to respond to NAC prior to RNU for UTUC in order to maximize its therapeutic benefit. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.6_suppl.475
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Differential expression of FOXF1 in bladder cancer metastases and association with established bladder cancer subtypes.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 2_suppl ( 2016-01-10), p. 464-464
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 464-464
    Abstract: 464 Background: FOXF1 is a transcription factor that may act as a tumor suppressor by interaction with p53. We identified FOXF1 to be highly differentially expressed in a discovery set of primary bladder cancers and matched nodal metastases. Here we study FOXF1 in preclinical models and define the association of FOXF1 with clinical bladder cancer phenotypes in several independent cohorts. Methods: Whole genome mRNA gene expression profiling (GEP) using Illumina HT12v3-4 chips was performed on paired primary tumors and nodal metastases from a cystectomy cohort. Among the top differentially expressed genes, FOXF1 was identified as a candidate regulator of cancer cell invasion. Murine orthotopic xenografts were established from human bladder cancer cell lines (UC-3, UC-14), and mRNA expression was assessed by real-time PCR. Four independent clinical cohorts with GEP data were subtyped as luminal, p53-like, or basal according to a validated gene expression signature (Choi et al., Cancer Cell2014). Associations between FOXF1 expression with survival after cystectomy (adjusted Cox models) and bladder cancer subtype (ANOVA) were assessed. High gene expression was defined as expression 〉 median. Results: In the initial discovery set, FOXF1 expression was 3.6-fold lower in nodal metastases than paired primary tumors (n = 33, p 〈 0.001). Among xenografts with nodal metastases, FOXF1 expression was 1.4-fold lower in the metastases (n = 9, p = 0.0886). In two clinical cohorts (MDA Discovery n = 73 and GSE13507 n = 55), high FOXF1 expression was associated with improved cancer specific survival (HR = 0.35, p = 0.046) and overall survival (HR = 0.45, p = 0.006), respectively. In two other cohorts (MDA Validation n = 57 and GSE32894 n = 93), FOXF1 was not associated with survival after treatment. In all four cohorts, FOXF1 was most highly expressed in tumors subtyped as p53-like (p ≤ 0.0024 for all cohorts). Conclusions: FOXF1 is differentially expressed between primary and metastatic bladder cancer lesions. Across multiple independent cohorts, FOXF1 is more highly expressed among p53-like tumors known to be resistant to neoadjuvant chemotherapy, suggesting that this may be a novel predictive biomarker.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.2_suppl.464
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...