Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 18 ( 2022-05-10), p. 1782-
    Abstract: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death] ) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21] ); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration ClinicalTrials.gov Identifier: NCT02795962
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 12 ( 2022-12), p. 3728-3740
    Abstract: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48] ); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28] ). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75] ), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95] ). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 770-780
    Abstract: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR] , 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163] ; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction 〈 0.01); no heterogeneity was observed for other stroke subtypes ( P interaction 〉 0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4137-4137
    Abstract: 4137 Background: Mutations affecting DNA Damage Repair (DDR) genes have been associated with clinical benefits from platinum-based chemotherapy (PBC) in ovarian and breast cancer. Mutations of DDR genes, including BRCA1/2, PALB2, ATM, ATR, CHK1, or RAD51, are found in around 15% of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, whether advanced PDAC patients harboring DDR gene mutations could benefit more from PBC has not been well established. In this study, we aimed to compare the prevalence of DDR gene mutations between advanced PDAC patients who benefited from PBC and those who did not. Methods: We retrospectively analyzed samples from patients with advanced PDAC who received PBC at our institution from 2008 to 2022. Patients with partial response or progression-free survival (PFS) 〉 6 months were considered responders, and those with progression disease as the best response were considered non-responders. Tumor molecular profiling was performed on tumor samples by Next Generation Sequencing (NGS) of DNA. Fisher’s exact test was used to compare DDR genomic alterations in responders vs. non-responders. Overall survival (OS) was defined as the time from the start of PBC to the date of death. PFS was defined as the time between the start of PBC and the first date of documented progression or death, whichever occurs first. Survival outcomes were estimated using Kaplan-Meier curves, and differences were tested using the long-rank test. Results: A total of 132 patients with advanced PDAC treated with PBC were included in this study. The median age at diagnosis was 55 years (range 27-79 years), and 71 (53.79%) patients were male. In this cohort, 88 (66.67%) patients were identified as responders. Tumor molecular profiling showed that among responders, 42 patients (47.7%) had genomic alterations in BRCA1/2 or PALB2, and 10 patients (11.3%) had alterations in other DDR genes. In contrast, only 17 patients (38.64%) showed DDR gene alternations among non-responders. Importantly, mutations in DDR genes are significantly associated with the responder group (OR=2.28; 95% CI 1.03-5.17, p=0.04). In line with these findings, patients with DDR gene mutations showed significantly longer PFS (median PFS 9.95 months) compared with patients without DDR gene mutations (median PFS 6.51 months) (HR= 0.57; 95%CI 0.39-0.85; p=0.005). Moreover, significantly longer OS was found in patients with DDR gene mutations (median OS 20.5 months) compared with those without DDR gene mutations (median OS 16.8 months) (HR=0.67; 95%CI 0.45-1; p=0.05). Conclusions: Genomic alterations in DDR genes are significantly associated with the benefit of PBC treatment in advanced PDAC patients. Our results argue in favor of using DDR genes as a decision-making tool for advanced PDAC patient stratification even before the stand-of-care chemotherapies.
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 582-582
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 582-582
    Abstract: 582 Background: Ampullary carcinoma (AC) is a rare heterogeneous group of diseases with an abysmal prognosis. Treatment options are limited, and the molecular landscape of this disease and its therapeutic implications have been incompletely explored. Here, we aim to provide a clinical and genomic characterization of AC and explore opportunities for precision oncology. Methods: Patients diagnosed with AC and treated at a single tertiary institution between 2010 and 2022 were reviewed. Molecular profiles were analyzed by applying an in-house exome-targeted panel or the FoundationOne CDx panel. Gene mutations were categorized into molecular pathways and potentially targetable alterations were classified according to the ESCAT scale. Overall survival (OS) and disease-free survival (DFS) were estimated by using the Kaplan-Meier method. Results: We included 64 patients with a median age of 66 years, 51.6% were women, most were classified as pancreatobiliary tumours (PB, 58.3%), followed by intestinal (INT, 33.3%) and mixed histologies (8.3%). 18.8%, 23.4%, 32.8% and 25.0% of the patients were diagnosed at stage I, II, III and IV, respectively. 81.2% of the patients were treated with surgery. The INT subtype was enriched in WNT pathway alterations (28.6 vs 6.2%, p=0.02) and showed a non-significant enrichment in the apoptotic pathway (57.1 vs 34.4%, p=0.08). Conversely, BP showed a non-significant enrichment in HRR pathway alterations (16.7 vs 54.5%, p=0.3). The frequency of KRAS mutations were similar in both subtypes (38.1 vs 37.5%). Potentially actionable molecular alterations were found in 46.7% of the patients (9 ERBB2, 8 HRD, 8 PI3KCA, 2 MSI, 2 BRAF, 2 PTEN and 1 KRAS G12C). Importantly, KRASwt tumours were enriched in potentially targetable alterations (ESCAT I-IIIA), including 20% ERBB2 amplification/mutations, 6% MSI and 3% BRCA1. 6 patients received matched targeted therapies during their disease course, 66% of which responded and 100% stable disease, with a median TTD of 7 months. Conclusions: More than 45% of AC harbor potentially targetable genomic alterations that may provide novel therapeutic opportunities and enhance personalized medicine in this rare disease entity.
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 2 ( 2023-01-17), p. 432-445
    Abstract: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%–50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA. Experimental Design: We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues. Results: This collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD. Conclusions: Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16302-e16302
    Abstract: e16302 Background: Approximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients present with advanced disease at diagnosis, with a 5-year survival rate of less than 5%. According to molecular profiling, mutations in KRAS have been described in 90% of PDAC patients, and correlated with poor prognosis. Nevertheless, the invasiveness of tumor biopsy and the difficulties in obtaining quality samples in some patients remains a concern. Circulating free DNA (cfDNA) is considered a surrogate marker of tumor burden and may also act as a prognostic factor that can be used independently from tumor biopsy. In this study, we aim to explore molecular prognostic biomarkers using plasma samples. Methods: Patients with metastatic PDAC harboring KRAS mutation in tissue samples and treated with first-line chemotherapy were identified at Vall d’Hebron University Hospital. Clinical features and plasma samples were collected before starting any treatment. DNA mutations were analyzed in plasma and compared with tissue samples. In plasma, detection of KRAS mutation and total cfDNA concentration were evaluated for clinical significance. A cfDNA minimum 100 genome equivalent threshold was proposed based on results and utility. A Chi-square test was planned to prove the independence between cfDNA levels and KRAS detection in plasma. Survival analysis was performed using the Kaplan-Meier method. Results: We included 33 PDAC patients with a median age of 66.1 years old, 57% were women. All of them were treated with gemcitabine and Nab-paclitaxel. At the final analysis cut-off, 31 patients had died . KRAS mutation was detected in 25 patients’ blood samples (75.8%) and cfDNA-High levels were considered for 20 patients (60.6%). 19 of 20 (95%) patients with cfDNA-High correlated with KRAS blood detection, showing significant dependence (p-value 0.001). Median overall survival (OS) was 10.5 months in the KRAS detected group compared with 22.6 months in the KRAS non-detected group (HR for death 4.70; confidence interval (CI) 1.70-12.98, p-value 0.002). Better separation was seen using cfDNA where median OS was 9.8 months in the cfDNA-High group compared with 21.0 months in the cfDNA-Low group (HR for death 5.38; CI 2.17-13.31, p-value 〈 0.001). Conclusions: Liquid biopsy can provide quality prognostic information in metastatic PDAC patients. On account of this, the cfDNA level is proposed as a prognostic factor. However, prospective cohorts to validate this information are needed.[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: 2022
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Cancer Treatment Reviews, Elsevier BV, Vol. 120 ( 2023-11), p. 102604-
    Type of Medium: Online Resource
    ISSN: 0305-7372
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2002084-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4101-4101
    Abstract: 4101 Background: Biliary tract cancer (BTC) is a heterogeneous group of diseases commonly diagnosed at advanced stages. Overall survival (OS) is the gold-standard primary endpoint in randomized controlled trials (RCT). However, the increasing use of subsequent lines of therapies and cross-over designs may confound the treatment effect. We therefore explored the use of progression free survival (PFS) as a surrogate endpoint of OS both at the trial-level and at the patient-level. Methods: For the trial-level correlation, we conducted a systematic review of RCTs in advanced BTC following the PRISMA guidelines. We searched PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from database inception to June 2022 and identified all randomized phase II/III trials testing systemic therapies for advanced BTC. We used a weighted linear regression to measure the correlation of log-transformed hazard ratios (HR) of OS and PFS based on trial size and calculated the surrogate threshold effect (STE). We used the IQWiG framework to define the strength of evidence. For the individual-level analysis, we included patients with advanced BTC treated with first and second line chemotherapy in the real-world RETUD registry. We estimated the correlation via the iterative multiple imputation method. Results: From a total of 1992 studies, we identified 32 RCTs including 70 treatment arms and 5140 patients that fulfilled the inclusion criteria. Twenty-three trials were performed in the first line setting and most were phase II RCTs (N = 23). We found a moderate correlation between OS and PFS ( R= 0.79, 95% CI 0.61-0.89). The slope of the regression line was 0.62±0.08, indicating that a 10% risk reduction in PFS will result in a 6.2%±0.8% improvement in OS. The STE was 0.69, suggesting that in a hypothetical trial of 400 patients, a PFS HR of 0.69 will likely result in a significant improvement on OS. Regarding the individual-level correlation, a total of 593 patients with advanced BTC were included. The median age of patients was 68y (IQR 59-74), most were males (54%) and received platinum-based chemotherapy (73.1%). In the first line setting, the median OS was 9.7 months (95% CI 8.7-10.5) and median PFS was 5 months (95% CI 4.5-5.5). We observed a strong correlation between PFS and OS ( r= 0.84, 95% CI 0.81-0.86). In the second line setting (N = 259), a similar correlation was observed to the first-line setting ( r= 0.76, 95% CI 0.72-0.8). Conclusions: At the trial-level, in this analysis treatment effects on PFS were moderately correlated with OS. A HR 〈 0.69 in PFS suggested that it would likely lead to a significant OS benefit in a hypothetical trial including 400 patients. At the individual-level, PFS and OS were strongly correlated in a real-world cohort. Future validation in patients treated in the context of randomized trials is warranted.
    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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4085-4085
    Abstract: 4085 Background: Actionable genetic alterations can be identified in over 50% of intrahepatic cholangiocarcinoma (iCCA). Since EMA approved Pemigatinib, a selective Fibroblast growth factor receptor 1-3 (FGFR1-3) inhibitor for the treatment of CCA with FGFR2 fusions or rearrangements, the screening of patients who may benefit from such targeted therapies is especially relevant. In addition, novel FGFR inhibitors that are effective for treatment of resistant mutant clones are under development. In patients with no available tissue for genomic profiling or at different timepoints after targeted therapy, NGS testing of circulating cell-free DNA (ccfDNA) would be the most convenient option. Hence, two important issues must be addressed: i) technical set-up and validation of detection of FGFR2 rearrangements in plasma, and ii) patient shedding in iCCA, in order to consider liquid biopsy for routine clinical care. Methods: We conducted a retrospective study in a cohort of 18 iCCA patients with known FGFR2 fusion or rearrangement events previously identified in tumor FFPE by NGS (FoundationOne CDx test). A custom-designed capture-based NGS panel for use in plasma or tissue (VHIO-iCCA test) was developed to detect FGFR2 rearrangements and other common altered genes in iCCA. After validating our VHIO-iCCA panel with fusion positive FFPE samples, a concordance study was conducted to evaluate the detection of FGFR2 fusion and rearrangements in matched-to-tissue timepoint plasmas. Finally, additional serial plasma samples taken during FGFR inhibitor treatment were also analyzed. Results: From the 18 rearrangement events previously detected with FoundationOne CDx, we were able to identify all 18 in FFPE samples and 15 in the paired plasma using our VHIO-iCCA panel, representing a 100% and 83% concordance, respectively. In the 3 discordant cases, no additional alterations were detected in plasma, indicating a lack of circulating tumor DNA (ctDNA) shedding. Serial sampling of these patients indicated persistent non-shedding. The analysis of fusion allele fraction (FAF) in serial plasma samples revealed that detection of fusion FGFR2 changed during treatment and correlated with best response. In general, patients with a stable FAF showed a SD, while patients which reduced FAF presented a PR. Conclusions: This extremely valuable set of cases has allowed us to validate our VHIO-iCCA panel to be used in tissue and plasma, and to determine that the sensitivity in plasma is 〉 80%, making this a feasible option to avoid tissue biopsies, whenever patients cannot undergo the procedure and even to aid in cancer monitoring. Patient shedding is high in iCCA, yet a fraction of patients may not find a useful resource in liquid biopsy. For those who shed ctDNA, monitoring through the FAF may guide clinical management of iCCA.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages