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  • 1
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    Online Resource
    Tumor/normal genomic profiling in patients with metastatic solid tumors identifies pathogenic germline variants of therapeutic importance.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 1501-1501
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 1501-1501
    Abstract: 1501 Background: Tumor molecular profiling via next-generation sequencing (NGS) is routinely utilized to direct patients toward clinical trials of targeted therapeutics. NGS testing of paired tumor/normal samples identifies incidental pathogenic germline variants (PGVs), having potential implications for patients and their families. Methods: From 2011-2018, 1,015 patients with metastatic, refractory solid tumors underwent targeted (1700 genes) exome and transcriptome sequencing of matched tumor/normal samples through the Michigan Oncology Sequencing program. Identified PGVs that conferred increased cancer risk or were associated with certain autosomal recessive conditions were reported to the treating oncologist. Chart reviews were conducted every 3 months to assess whether PGV identification impacted treatment decision making. Results: 169 PGVs were identified in 160 unique patients (15.8% of cohort). 69 PGVs (41%) harbored a clear somatic second hit event in the tumor. PGVs associated with defects in double-strand DNA repair ( BRCA1, BRCA2, ATM, PALB2, BRIP1) or DNA mismatch repair ( MLH1, MSH2 and PMS2) were identified in 49 patients (5% of cohort, 31% of patients with PGVs), 37 of which had not previously been identified. 14 PGVs in DNA double-strand repair and 7 PGVs in DNA mismatch repair were identified in cancer types not commonly associated with hereditary breast ovarian cancer or Lynch syndromes, including cancers of unknown primary origin and sarcomas. 7 patients received a PARP inhibitor (PARPi), 3 patients received an immune checkpoint inhibitor (ICI) and 1 patient received both PARPi and ICI therapy on the basis of a PGV in DNA repair. 6 patients achieved clinical benefit, defined as time on treatment ≥ 6 months. A patient with cancer of unknown primary origin and PGV in MSH2 achieved exceptional response to ICI therapy, with complete response ongoing and lasting 23 months. Conclusions: Targeted NGS of matched tumor/normal samples identified PGVs in about 1 in every 6 patients with metastatic solid tumors. Approximately 40% of PGVs are associated with a somatic second hit in the tumor, supporting their role in tumor pathogenesis. Unexpected PGVs with therapeutic implications are identified in patients with diverse cancer types, providing opportunities to use targeted therapies with potential for significant clinical benefit. Given this finding, testing for PGVs in DNA repair genes should be considered in all patients with metastatic solid tumor malignancies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.1501
    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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  • 2
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    Multicenter retrospective study of clinical genetic testing in patients with sarcoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 10511-10511
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 10511-10511
    Abstract: 10511 Background: Sarcomas are rare and diverse malignancies with a subset developing in the context of heritable cancer predisposition syndromes. Data surrounding the frequency of inheritance and patient/genomic findings are limited. We aimed to describe the characteristics of patients with sarcoma referred for clinical genetic testing and to determine the prevalence of pathogenic/likely pathogenic germline variants (PGV/LPGV). Methods: We performed retrospective chart reviews of patients with sarcoma referred to Michigan Medicine Cancer Genetics Clinic between 12/2006 and 1/2020 and Vanderbilt Hereditary Cancer Clinic between 1/2005 and 1/2019. Reviewers obtained medical/family history, cancer phenotype, and results of germline genetic testing. Descriptive analyses were performed to assess the prevalence of germline variants classified as pathogenic/likely pathogenic according to American College of Medical Genetics criteria. Associations with clinical factors were tested for using Fisher’s exact test or Wilcoxon rank-sum test. Results: One-hundred sixteen patients with sarcoma underwent genetic evaluation during a 15-year period. Mean age at time of visit was 46 years (SD, 17.6 years; range, 1-80 years). Sixty-nine patients (59%) were female. The most common reasons for referral were personal history of multiple malignancies (n = 69, 59.4%), first degree relative (FDR) with malignancy (n = 67, 57.7%) and young age at diagnosis (age ≤ 18, n = 18, 15.5%). Forty-eight patients (41.4%) had both a history of multiple malignancies and a FDR with a malignancy. Eight patients had a FDR with sarcoma (6.9%). Of the 110 patients who underwent germline testing, 53 patients (48.2%) had a PGV/LPGV. Identified germline variants and frequencies are listed in the Table. There was no statistical significance between young age at diagnosis, history of personal malignancies, FDR with sarcoma, FDR with one or more malignancies, or multiple FDRs with malignancy and presence of a PGV/LPGV. Conclusions: In this multicenter study, approximately half of patients with sarcoma referred for cancer genetic testing had a PGV/LPGV associated with hereditary predisposition to cancer. There was no identified positive predictive factor for germline variants. Though TP53 was the most common, over 20 genetic variants were identified, supporting the consideration of multigene panel testing. Our study is limited to patients who were both referred to and attended genetic evaluation. Yet, the high frequency of pathogenic germline variants observed highlights the necessity for further investigation of the prevalence of and predictive factors for germline mutations in all sarcoma patients. Identified germline variants. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.10511
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Oncologists’ use of tumor sequencing findings and patient derived benefit.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e13016-e13016
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e13016-e13016
    Abstract: e13016 Background: Despite increasing use of tumor genomic sequencing in clinical oncology, there is currently limited understanding of how oncologists interpret and apply this information to a patient’s clinical management. Methods: We surveyed oncologists who referred patients with refractory cancers to the Michigan Oncology Sequencing (MI-ONCOSEQ) program which uses integrative clinical sequencing to detect multiple classes of somatic and germline molecular aberrations including point mutations, amplifications, insertions/deletions, gene fusions, and outlier gene expression from June 2014-February 2015. Patients were also surveyed approximately 2 weeks after notification of completion of sequencing. In addition, we conducted chart reviews to ascertain how many patients’ clinical management was changed or derived clinical benefit as a result of sequencing. Results: Forty-three oncologists (37% female, 98% academic medical center practice), referring 112 patients ( M = 2, range: 1-9) completed the survey (response rate = 93%). Oncologists reported an intention to change 22% of patients’ treatment plans on the basis of sequencing results, with referral to a clinical trial (N = 12; 50%) as the most frequently endorsed intended change. However, few patients (N = 9, 38%) had an actual change in clinical management. Barriers identified included patient factors, ineligibility for identified treatment, and loss to follow-up/deceased. Of the 57 patients who completed post-sequencing surveys, 34 (60%) reported that results of sequencing had not been disclosed. However, patient records had documentation that results disclosure had indeed taken place in 41% of cases. Conclusions: Although expectation of enrollment in clinical trials is frequently proposed as the indication for genomic sequencing, practice barriers remain. These include lack of access to studies, severity of patient illness and challenges to effective communication of results.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e13016
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Clinical application of comprehensive next generation sequencing in the management of metastatic cancer in adults.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 101-101
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 101-101
    Abstract: 101 Background: Next generation sequencing (NGS) platforms are frequently utilized in the care of patients (pts) with metastatic cancer to identify tumor genomic alterations that may serve as therapeutic targets. Biomarker driven clinical trials, such as NCI-Molecular Analysis for Therapy Choice (MATCH) and Targeted Agent and Profiling Utilization Registry (TAPUR) have augmented clinicians’ ability use this strategy in clinical practice. Methods: From 2011-2015 over 500 adult pts with metastatic solid tumors of diverse lineage underwent biopsy for whole exome and transcriptome sequencing of tumor and matched normal sample through the Michigan Oncology Sequencing Center (Mi-Oncoseq). Genomic alterations identified were reviewed at Precision Medicine Tumor Board and tiered according to their clinical relevance. Alterations were also classified as being identifiable or not identifiable by a commercially available NGS assay such as Oncomine Focus or FoundationOne. Results: Genomic alterations identified by Mi-Oncoseq provided rationale for enrollment in a clinical trial in 72% (n = 360) of cases. The percentage of pts who did receive therapy informed by NGS results increased over time (5% in 2012 versus 11% in 2015). 11% of pts (n = 55) had a pathogenic germline variant (PGV) conferring increased cancer risk identified, none of which were known prior to study entry. Numerous pts had clinically relevant molecular alterations identified by Mi-Oncoseq that would not have been identifiable utilizing targeted NGS assays, including PGVs and activating/deleterious gene fusions. Conclusions: Comprehensive NGS, including DNA and RNA sequencing, readily identifies potentially actionable alterations in the vast majority of pts beyond what is observed with use of targeted NGS platforms. Observed modest increase in utilization of NGS results to direct subsequent therapy over time is due to clinician employment of this strategy earlier in the therapeutic algorithm, increased availability of biomarker driven clinical trials and changes in physician referral patterns. Comprehensive NGS identified many unanticipated PGVs of clinical importance for pts and their families. Clinical trial information: HUM00067928.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.101
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Use of comprehensive next-generation sequencing to identify pathogenic germline variants with therapeutic relevance in metastatic breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 10527-10527
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 10527-10527
    Abstract: 10527 Background: Among patients with early-stage breast cancer, approximately 6-10% have a pathogenic germline variant (PGV) conferring inherited cancer predisposition. In contrast, few studies have explored the frequency and types of PGVs identified in patients with metastatic breast cancer (MBC); therefore, additional data is needed. Methods: From 2011-2020, 278 patients with MBC underwent fresh tumor biopsy and blood sample collection for paired tumor/normal DNA (targeted exome capture with analysis of 1700 genes) and RNA (tumor transcriptome) sequencing through the Michigan Oncology Sequencing (Mi-ONCOSEQ) program. Somatic and germline alterations were annotated and classified according to degree of clinical actionability with results returned to treating oncologists. Retrospective chart review was performed to determine if: 1) a PGV was identified prior to Mi-ONCOSEQ testing, 2) patients met National Comprehensive Cancer Network (NCCN) guideline criteria for genetic testing on the basis of personal or family cancer history and 3) patients received subsequent therapy informed by a PGV. Results: Forty-eight of the 278 patients (17.3%) had at least one PGV identified, with a total of 50 PGVs identified in this cohort. Only twelve of these PGVs (24%) had been identified prior to Mi-ONCOSEQ testing. The most frequent PGVs identified were in CHEK 2 (n = 9, 18%), MUTYH (n = 6, 12%), BRCA 1 (n = 5, 10%), BRCA2 (n = 5, 10%), ATM (n = 4, 8%) and PALB2 (n = 4, 8%). Somatic loss of heterozygosity events (LOH) occurred in 30 of the 50 cases with PGVs identified (60%). LOH events were observed in 83.3% of BRCA1, BRCA2, ATM and PALB2 PGVs, but were less frequently observed with CHEK2 (33.3%) and MUTYH (66.7%). Two hundred sixteen out of 278 patients (77.7%) in this cohort met NCCN criteria for genetic testing, although six patients with a PGV identified (CHEK2: n = 5; MUTYH: n = 1) did not meet NCCN criteria. Twenty-nine PGVs identified (58%) had potential therapeutic relevance and 11 patients (22.9%) received targeted therapy based on the PGV. Conclusions: The frequency of PGVs identified in this cohort is nearly double the frequency reported for patients with early-stage disease, suggesting that certain PGVs may confer worse prognosis. CHEK2, the most frequently identified PGV, was less likely to have an identifiable LOH event. The direct role of CHEK2 PGVs in tumor pathogenesis is uncertain, but other mechanisms of silencing the wild type allele must be considered. Despite the majority of patients meeting NCCN criteria for genetic testing, those with PGVs in CHEK2 were less reliably identified by this mechanism. The majority of PGVs identified were of potential therapeutic relevance, supporting the recommendation for genetic testing in all patients with MBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.10527
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Clinical impact of high-throughput sequencing in patients with advanced cancer: Lessons learned from the Michigan Oncology Sequencing Center.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 11057-11057
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 11057-11057
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.11057
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 7
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    MammaPrint Index as a predictive biomarker for neoadjuvant chemotherapy response and outcome in patients with HR+HER2- breast cancer in NBRST.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 521-521
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 521-521
    Abstract: 521 Background: Hormone receptor positive (HR+), HER2- early stage breast cancer (ESBC) is a heterogeneous disease that has shown lower response to neoadjuvant chemotherapy (NCT) compared with other clinicopathologic subtypes. Genomic profiling may help inform neoadjuvant treatment decisions for ESBC by predicting likelihood of pathological complete response (pCR) or chemosensitivity. The 70-gene MammaPrint (MP) test classifies ESBC patients as having a Low or High Risk of distant metastasis. In the ISPY2 trial, further stratification of MP High Risk into High 1 (H1) or High 2 (H2) improved prediction of chemosensitivity, with significantly higher pCR rates in H2 vs. H1 tumors, particularly in response to immune therapy. Here we evaluate the utility of H1/H2 risk as a biomarker for chemosensitivity and 5 year distant-metastasis free survival (DMFS) in NCT treated patients from the Neoadjuvant Breast Registry Symphony Trial (NBRST). Methods: NBRST (NCT01479101) is an observational prospective study that included 1069 patients with ESBC who received neoadjuvant therapy. Patients with HR+HER2-, MP High Risk tumors who received NCT were included in this analysis (n = 327). Patients were further stratified into H1 (score ≤ 0, 〉 -0.57) or H2 (score ≤ -0.57) groups. Differences in pCR between MP High Risk subcategories were assessed by two-sided proportional z-test. Differences in DMFS was evaluated by Kaplan Meier analysis and log-rank test. Results: MP classified 198 (61%) patients with H1 tumors and 129 (39%) patients with H2 tumors. Age, tumor stage, and lymph node status were comparable between both groups. However, there was a higher proportion of Grade 3 tumors in the H2 group. A significantly higher percentage of pCR was achieved in H2 tumors (30/129; 23%) vs. H1 tumors (12/198; 6.1%) (p 〈 0.001). Median follow-up was 5.3 years. The 5-year DMFS (% [95% CI]) was significantly worse for patients with H2 tumors (64.8 [55.9 – 75.1] ), with most events occurring early ( 〈 3 years), compared with H1 tumors (77.1 [70.4 – 84.3] ; p = 0.012). Patients with H1 tumors that achieved pCR had improved 5-year DMFS (81.8 [61.9 – 100]) compared to H1 tumors that did not achieve pCR (76.8 (69.9 – 84.4; p = 0.009). Patients with H2 tumors that had a pCR demonstrated significantly better 5-year DMFS (80.7 [65.3 – 99.8] ) than patients with residual disease (60.2 [50.1 – 72.4]; p = 0.009). Conclusions: These data suggest MammaPrint predicts pCR in HR+HER2- BC patients, with H2 risk tumors exhibiting higher chemosensitivity than H1 tumors. Patients with either H1 or H2 tumors that achieved pCR had similar outcomes, which were significantly improved compared to those with residual disease. Notably, the worst outcomes were observed among patients with H2 risk and residual disease; it should be investigated whether addition of immune therapy to standard NCT would enhance the pCR rates in this patient population. Clinical trial information: NCT01479101 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.521
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Comparing the prognostic and predictive utility of serum thymidine kinase 1 and CA 15-3 in patients with hormone receptor positive metastatic breast cancer starting first-line endocrine therapy in SWOG S0226.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 1076-1076
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 1076-1076
    Abstract: 1076 Background: Serum levels of thymidine kinase 1 activity (TKa), a fundamental enzyme in DNA synthesis and cellular proliferation, are prognostic of benefit from endocrine therapy (ET) in patients (pts) with hormone receptor positive (HR+) metastatic breast cancer (MBC) who participated in SWOG S0226, a prospective randomized trial comparing anastrozole vs. anastrozole and fulvestrant given in 4 week cycles. The assay for TKa (DiviTum TKa) was FDA approved in July 2022 for monitoring of postmenopausal HR+ MBC pts. The assay for circulating MUC1, CA 15-3, is routinely utilized in monitoring of pts with MBC. We compared the prognostic and predictive utilities of CA 15-3 and TKa in pts from S0226. Methods: TKa was measured in 1725 sera from 432 pts while CA 15-3 was measured in 1298 sera from 326 pts at baseline (BL), cycles 2, 3, 4 and 7. Prespecified cutoff levels of ≥ 250 DuA and ≥ 30 U/mL were considered high for TKa and CA 15-3 respectively. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier and Cox regression stratified by prior adjuvant tamoxifen use. To examine markers over time, a landmarked Cox regression analysis was done starting at initiation of Cycle 4. BL and recent (Cycle 3 if available, otherwise Cycle 2) markers were assessed for simultaneous prediction of subsequent PFS and OS. Results: BL TKa was elevated in 190/432 (44%) and CA 15-3 was elevated in 254/326 (78%). Agreement between assays was 53%. Pts with high versus low BL TKa had significantly worse PFS (median 11.6 vs. 17.2 months, HR = 1.68, 95% confidence interval (CI) 1.37-2.06) and OS (median 34 vs. 58 months, HR = 2.16, 95% CI 1.73-2.70) whereas pts with high versus normal BL CA 15-3 had no significant difference in PFS (median 13.6 vs. 16.1 months, HR = 1.23, 95% CI 0.93-1.62) but worse OS (median 45 vs. 66 months, HR = 1.82, 95% CI 1.30-2.53). A multivariable Cox model with both markers shows only TKa as being prognostic for PFS (TKa HR = 1.61, 95% CI 1.28-2.03; CA 15-3 HR = 1.21, 95% CI 0.91-1.59), but both prognostic for OS (TKa HR = 2.09, 95% CI 1.61-2.71; CA 15-3 HR = 1.70, 95% CI 1.22-2.38). In the landmarked multivariable analysis, positive TKa at BL was a strong predictor of PFS (HR = 1.65, 95% CI 1.28-2.14), but recent TKa was not (HR = 1.25, 95% CI 0.93-1.68). In contrast, positive CA15-3 at BL was not a predictor of PFS (HR = 0.73, 95% CI 0.46-1.17), but recent CA15-3 was (HR = 1.97, 95% CI 1.26-3.06). Conclusions: BL TKa is highly prognostic in pts with HR+ MBC initiating first-line systemic ET, with low BL TKa conferring superior prognosis. In contrast, CA 15-3 is only modestly prognostic at BL, but is prognostic after 3 cycles of treatment. These hypothesis-generating data suggest further study is needed to determine how these biomarkers should be employed in a complementary manner to monitor response to systemic therapy in HR+ MBC. Clinical trial information: NCT00075764 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.1076
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial
    Elsevier BV ; 2023
    In:  The Lancet Vol. 401, No. 10387 ( 2023-05), p. 1499-1507
    Details
    In: The Lancet, Elsevier BV, Vol. 401, No. 10387 ( 2023-05), p. 1499-1507
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(23)00510-X
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    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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  • 10
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    Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis
    Elsevier BV ; 2022
    In:  The Lancet Vol. 400, No. 10349 ( 2022-07), p. 359-368
    Details
    In: The Lancet, Elsevier BV, Vol. 400, No. 10349 ( 2022-07), p. 359-368
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(22)01109-6
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    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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