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  • 1
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    Patient (pt) characteristics, treatment patterns, outcomes and prognostic factors in plasmacytoid urothelial carcinoma (PUC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e16007-e16007
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e16007-e16007
    Abstract: e16007 Background: PUC is uncommon and highly aggressive, with limited data on treatment patterns, outcomes and prognostic factors. We hypothesized that PUC is associated with clinical under-staging, poor outcomes and lack of chemotherapy (CT) response. Methods: We conducted a retrospective review of pts with UC and plasmacytoid component (PUC), seen in our institution (2000 - 2018). Demographic and clinicopathologic data, treatment modalities, pathologic complete/partial response (pCR, pPR) to neoadjuvant CT (NAC), and overall survival (OS) from diagnosis and surgery (Sx) were captured. T-test, chi-square, and Cox-regression were used to explore potential prognostic associations. OS was estimated with KM method. Results: We identified 63 consecutive pts (51 men) with available data for analysis. Median age at diagnosis was 67 (44-89). During initial diagnostic workup, 32 (51%) pts had extravesical disease (cT3:24, cT4:8) and 23 (36.5%) hydronephrosis at imaging. Overall, 39 (62%) pts underwent Sx with curative intent, 25 (39.6%) were pre-treated with cisplatin-based NAC; adjuvant CT was given to 15 (24%). The remaining pts pursued bladder-sparing and/or palliative approaches. At time of Sx, 17/39 (43.6%) pts had pathologic upstaging, 10 (25.6%) had positive margins and 19 (48.7%) pN+ stage. In the NAC pt subset (25 pts), 5 (20%) had progression on scans, 19 (76%) had Sx; 2 pts had pCR (10.5%), 1 had pPR, 6 (31.5%) had pathologic upstaging. In the entire cohort, median follow-up was 8 months. Median OS was 20.7 months from diagnosis and 23.6 months from Sx. NAC was not significantly associated with longer OS (from Sx) (HR 1.53, 95%CI 0.16-15, p = 0.715) and the same was true for adjuvant CT (HR 0.64, 95%CI 0.1-4, p = 0.630). 15/39 pts recurred after Sx (38.4%), with 9/15 (60%) having peritoneal/retroperitoneal involvement. Conclusions: PUC frequently presented with advanced stage at diagnosis and demonstrated poor NAC response, frequent upstaging, positive margins and pN+ stage at Sx. More than half of patients who recurred after Sx, presented with (retro)peritoneal disease. Studies evaluating molecular biomarkers and drivers in PUC, and prospective clinical trials are being pursued.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e16007
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Perioperative blood transfusion and postoperative outcomes in patients undergoing radical cystectomy for bladder cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17012-e17012
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17012-e17012
    Abstract: e17012 Background: Perioperative blood transfusion (PBT) has been associated with worse outcomes in surgical oncology across tumor types. We report our institutional experience of postoperative outcomes related to PBT utilization, in patients (pts) with bladder cancer (BC) treated with radical cystectomy (RC). We hypothesized that PBT is associated with worse clinical outcomes. Methods: Pts with BC treated with RC were retrospectively identified. Clinicopathologic and peri/post-operative data were extracted. PBT was defined as red blood cell transfusion during RC or postoperative hospitalization. Overall survival (OS, diagnosis to death) and recurrence free survival (RFS, RC to recurrence/death) were estimated with the KM method. T-test, χ 2 and log-rank test were used for group comparison analysis. Univariate/multivariate logistic (LR) and Cox regression (CR) were used to identify variables associated with dependent dichotomous outcomes and OS/RFS, respectively. Results: 784 consecutive pts (78% men; median age 67) were identified. At least one post-operative complication (POC) occurred in 407 (52%) pts; most common were pyelonephritis and sepsis (11% each). PBT was administered to 238 pts (30%). Those with PBT had a higher proportion of POCs (35% vs 28%, p = .02). Median follow-up, OS and RFS were 66 (95% CI: 60 - 72), 94 (95% CI: 79 - 109) and 66 months (95% CI: 50 – 82), respectively. Pts who received PBT had shorter OS (51 vs 130 months, p 〈 .001) and RFS (27 vs 86 months, p 〈 .001). In multivariate LR and CR, PBT was independently associated with higher odds of POCs (OR 1.5, 95% CI: 1.03 – 2.2, p = .03), length of hospital stay (LOS) 〉 10 days (OR 2.0, 95% CI 1.1 – 3.5, p = .02), shorter OS (HR 1.6, 95% CI 1.2-2.0, p = .001), and RFS (HR 1.5, 95% CI 1.2 - 1.9, p = .001), after adjustment for other relevant clinicopathologic variables (age, gender, performance status, neoadjuvant chemotherapy, baseline hemoglobin, open/robotic approach, pT/N stage, surgical margins, lymphovascular invasion at RC, variant histologies). Conclusions: Pts who received PBT had higher odds of POC, longer LOS and poor outcomes after RC. This is hypothesis-generating due to inherent study limitations. Further studies are needed to validate this finding, explain underlying mechanisms and explore putative interventions to improve outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e17012
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Sarcomatoid urothelial carcinoma: Oncologic outcomes from a tertiary center and SEER-Medicare data.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17033-e17033
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17033-e17033
    Abstract: e17033 Background: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive bladder cancer variant with little evidence regarding prognostic characteristics and response to neoadjuvant chemotherapy (NAC). In this study, we delineate oncologic outcomes in patients with SUC after radical cystectomy (RC), presenting data from our institutional database and SEER-Medicare. Methods: We retrospectively queried our institutional database to identify consecutive patients with cT2-4 SUC and conventional (non-variant) UC (CUC) who underwent RC (2003-2018). SEER-Medicare database was also searched for patients with cT2-4 SUC (2004-2015). Clinicopathologic/treatment data were captured. Overall survival (OS – diagnosis to death) was estimated with the Kaplan-Meier method. T-test, χ 2 test and log-rank test were used for group comparison analysis. Factors significant in univariate analysis for OS were included in the multivariate (MVA) Cox proportional hazards model. Results: Institutional RC database yielded 38 patients with SUC and 287 with CUC, while 190 patients with SUC were identified from SEER-Medicare [83 (44%) had RC] . Platinum-based NAC was given to 17/38 (45%), 162/287 (56%) and 26/83 (31%) patients, respectively. Institutional patients with SUC had significantly higher rates of pT3/4 disease at RC (66% vs. 35%, p 〈 .001) and lower rates of complete pathologic response (ypT0N0) following NAC (6% vs 35%, p = .02). Median OS in patients who had RC was significantly inferior in our institutional SUC vs. CUC group (20 vs. 121 months, p 〈 .001) and 21 months in the SEER-SUC cohort. No significant difference in OS was identified between NAC+RC vs. RC alone, both in the institutional (17 vs. 20 months, p = 0.66) and SEER-SUC cohort (24 vs. 20 months, p = 0.56). In MVA for the entire institutional cohort (SUC+CUC combined), SUC was independently associated with worse OS, when adjusted for advanced age, pT/N stage, performance status, NAC, lymphovascular invasion, surgical margins (HR, 95% CI: 2.3, 1.4 - 3.8, p = .001). Five patients had an abdomino-pelvic cystic recurrence, with median time to recurrence 〈 5 months. Conclusions: Patients with SUC treated with RC had high rates of extravesical extension, poor response to platinum-based NAC and worse OS compared to patients with CUC. Data from SEER showed a comparable OS to our SUC cohort. NAC was not associated with improved OS in any SUC cohort (institutional or SEER). A unique pattern of rapid abdomino-pelvic cystic recurrence, mimicking post-RC abdominal fluid collections, was also identified.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e17033
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Sarcomatoid urothelial carcinoma (SUC): A single-institution experience of oncologic outcomes and recurrence patterns.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 465-465
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 465-465
    Abstract: 465 Background: SUC is a rare histology with aggressive behavior. We evaluated outcomes and recurrence patterns of patients (pts) with SUC, in comparison with conventional urothelial carcinoma (CUC). Methods: We retrospectively assessed our radical cystectomy (RC) database to identify pts with cT2-4 SUC (any %) or CUC, at RC or transurethral resection specimens. Clinicopathologic/treatment data were captured and compared with t and χ 2 tests, as appropriate. Overall survival (OS; diagnosis to death) and recurrence-free survival (RFS; RC to recurrence or death) were estimated (KM method). Significant factors in univariable (UVA) Cox regression for OS were included in multivariable analysis (MVA). Results: We identified 38 consecutive pts with cT2-4 SUC and 287 with CUC (2003-2018); 17 (45%) and 162 (56%) received neoadjuvant chemotherapy (NAC). The primary non-mesenchymal component was urothelial in all SUC cases. SUC had higher rates of pT3/4 (66% vs. 35%, p 〈 .001) but comparable rates of pN+ disease (26% vs. 20%, p = .38). Complete response (ypT0N0) after NAC was lower for SUC (6% vs. 35%, p = .02). Median follow-up was 73.6 months (95%CI 62.6 – 84.7). Median RFS and OS was inferior among pts with SUC (9.4 vs 109.8 months, p 〈 .001, 19.7 vs. 130.4 months, p 〈 .001 respectively). On MVA, SUC was independently associated with worse OS ( Table). Of 17 (45%) pts with SUC who recurred post-RC, 5 presented with abdomino-pelvic cystic masses, with an average time to recurrence 〈 5 months. Conclusions: SUC was associated with high rates of extravesical spread at RC and worse NAC response, RFS and OS, vs. CUC. Development of abdomino-pelvic fluid collections should raise suspicion of recurrence among pts with this histology. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.465
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Micropapillary urothelial carcinoma (mpUC): A comparative analysis of oncologic outcomes compared to conventional urothelial carcinoma (CUC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 459-459
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 459-459
    Abstract: 459 Background: MpUC is a rare variant associated with adverse outcomes. We describe our institutional experience and compare clinicopathologic features and survival between patients with mpUC and CUC. Methods: Patients with mpUC or CUC at radical cystectomy (RC) or transurethral resection of bladder tumor were identified from a retrospective institutional RC database. Clinicopathologic/treatment data were extracted and compared using T-test and χ 2 test. Recurrence free survival (RFS) and overall survival (OS) from RC to first recurrence or death were estimated using the KM method. Factors identified as significant in univariable (UVA) Cox regression analysis for OS were included in multivariable analysis (MVA). Results: 64 consecutive patients with mpUC and 457 with CUC were identified (2003 - 2018); 36 (56%) and 188 (41%) received neoadjuvant chemotherapy (NAC). MpUC had higher incidence of pT3/4 (41% vs. 28%) or pN+ disease (39% vs. 17%), carcinoma in-situ (52% vs. 24%) and lymphovascular invasion (LVI, 39% vs. 16%) at RC, compared to CUC (all p 〈 0.05). Rates of ypT0N0 after NAC were comparable between groups (25% vs. 35%, p = 0.26). Median follow-up was 62 months (95% CI 55.4 – 68.3). 5-year RFS was 24% (mpUC) vs. 58% (CUC), p = 0.001. 5-year OS was 40% (mpUC) vs. 69% (CUC), p = 0.001. MpUC histology was not independently associated with OS after adjusting for pT stage, node ratio (# nodes +/ # nodes removed) and ECOG status (Table). Conclusions: Patients with mpUC presented with advanced stage at RC, while they showed inferior RFS and OS, when compared to CUC. However, rates of pathologic response to NAC were comparable to CUC and mpUC was not associated with OS in MVA. Further studies are needed to define the optimal management of this variant. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.459
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Characterization of human bladder cancer patient-derived xenograft in vivo and in organoids.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. 479-479
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 479-479
    Abstract: 479 Background: To establish and molecularly characterize a human bladder cancer patient-derived xenograft (PDX) in vivo and in an organoid system derived from the PDX for preclinical studies. Methods: Two-mm3 bits of urothelial carcinoma originated from muscle invasive disease excised in cystectomy were implanted subcutaneously into male severe combined immunodeficient mice to establish PDXs. Established PDXs (CoCaB 1) were passaged subcutaneously in SCID mice and histopathology of each passage was compared with the originating tumor. Tumor size was measured weekly by caliper to determine the growth rate of PDXs from early (P1/P2) through late passage (P8/P9). Representative early and late passages were collected for organoid establishment. For both early and late passages, proliferation was assessed by Ki67 in PDXs and organoids, and cell cycle analysis and MTS assay specifically in organoids. RNA sequencing was performed to compare the fidelity of PDX and organoids vs. primary tumor. Results: Histologically, 16 of the 16 (100%) PDXs generated from early through late passage (1-2 tumors per passage) were similar to the original high-grade urothelial carcinoma. In vivo, the latency of PDX establishment decreased upon passage (9 weeks to take in early P1/2 vs. 2 weeks to take in late P8/9) and the growth rate increased upon passage. Concordantly, Ki67 proliferation index increased from 40% in P1 to 95% in P8 and was positively correlated with increasing passage (Spearman R=0.804, p=0.001). Similarly, in organoids, late passage demonstrated a shorter growth doubling time, higher Ki67 proliferation index, and faster progression through cell cycle. Transcriptional analysis showed that the PDX contained 81-92% human transcripts, whereas organoids contained 〉 99% human transcripts. Conclusions: Bladder cancer PDXs histologically represented the originating disease. PDX and organoid systems demonstrated concordant increase in proliferation upon serial passages, suggesting clonal selection may take place in this aggressive tumor type. Despite more mouse stromal content in PDX, PDX and organoid represent two independent model systems with highly similar biological responses that allow therapeutic studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.6_suppl.479
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Bladder Cancer Multidisciplinary Clinic (BCMC) model: Impact on imaging, pathology and treatment recommendations.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4537-4537
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4537-4537
    Abstract: 4537 Background: Despite guideline-based standard of care recommendations in BC and upper tract urothelial carcinoma (UTUC), treatment remains variable across US. Experts recommend focusing BC care in tertiary centers. We hypothesized that a BCMC model, with expert central pathology and radiology review, may result in changes in corresponding reports, and, thus, treatment recommendations. Methods: Our BCMC clinic format includes simultaneous consultation with Urologic, Medical and Radiation Oncology, with real time expert genitourinary pathology and radiology review. We retrospectively assessed the concordance between outside (pre-BCMC) imaging & pathology review and BCMC review. Differences between pre- and post- BCMC recommendations on management were also assessed; descriptive statistics were used. Results: We identified 233 BC/UTUC patients (pts) referred to BCMC. Complete radiographic and pathologic data were available for 209 pts. Median age at time of evaluation was 68 (27-93) and 85% were PS ECOG 0-1. After BCMC review of outside records, 112 (53.6%) imaging and/or pathology changes were noted, with 57 (27%) pts upstaged. Overall, imaging interpretation was changed in 25% of cases, and 20% of pts were upstaged. BCMC pathology review resulted in changes in 59 (28%) pts. Among those, 42 (71%) had histologic subtype addition or change, 9 (15%) had LVI/CIS status change, and 2 (3.4%) had low to high grade conversion. In terms of pathology staging, 7 (12%) were downstaged, and 5 (8.5%) upstaged. Further diagnostic work-up was recommended in 71/209 (34%) pts, resulting in upstaging in 11/71 (15.5%) of cases. Pre- and post- BCMC-recommended treatment modality differed in 55/209 (26%) pts, while a new treatment modality was added in 28/209 (13%) pts. These recommendations were followed 91.4% of the time (191/209 pts). Conclusions: BCMC initiation at our institution resulted in imaging and/or pathology diagnostic changes in almost half of cases, with approximately a quarter of pts being upstaged. Findings reveal the importance of expert radiology and pathology review in BC. Further study is needed to confirm the proposed benefits and impact of BCMC on treatment response and outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4537
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Bladder cancer rapid autopsy: A mechanism for collecting metastatic tumor tissue and establishing xenograft models of metastatic disease.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. 478-478
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 478-478
    Abstract: 478 Background: Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. We established a bladder cancer rapid autopsy program to systemically acquire metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods: Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were collected and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each patient. Results: We have performed 10 bladder cancer rapid autopsies to date, and have acquired 105 metastatic and 45 normal specimens. The pathological subtypes of patients include urothelial cell carcinoma (5/10), squamous cell carcinoma (3/10), and plasmacytoid variant of urothelial carcinoma (2/10). The cohort has been treated BCG only (1/10), chemotherapy (3/10), and chemotherapy and immune checkpoint inhibitors (6/10). The leading site of metastasis was the liver (7/10) and lung (7/10), followed by lymph node (5/10), bone (5/10), intestine (4/10), and omentum (2/10). Half (5/10) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from two independent metastases (omentum – CoCaB 14.1 and liver –CoCaB 14.2) from the same patient were successfully developed. Conclusions: This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of advanced disease.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.6_suppl.478
    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
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