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  • 1
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    A single-arm, phase II study of autophagy modulation using hydroxychloroquine in addition to encorafenib and cetuximab or panitumumab in metastatic BRAF-mutated colorectal cancer refractory to standard therapy.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. TPS262-TPS262
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. TPS262-TPS262
    Abstract: TPS262 Background: BRAF mutations drive 5-10% of colon cancers. BRAF + EGFR inhibition with encorafenib + cetuximab is standard second-line therapy, per the BEACON trial, but responses are short-lived. Autophagy induction is implicated as a mechanism for this acquired resistance to therapy. Preclinical models have shown that BRAF inhibition leads to increased ATF4 phosphorylation and an overreliance on oxidative phosphorylation, both markers of autophagy induction. Use of hydroxychloroquine (HCQ), an antimalarial agent with anti-autophagy activity, reduces such markers and improves the cellular metabolic profile. This was confirmed clinically in the BAMM trial, a phase I/II study in which patients with advanced BRAF-mutated melanoma received dabrafenib, trametinib and HCQ (Mehnert JM et al, Clin Cancer Res 2022). This study asks a similar question in advanced, BRAF-mutated colon cancer, of whether autophagy inhibition overcomes acquired resistance to BRAF inhibition. Methods: This is a Phase II, single-arm, open-label study to be conducted at Robert H. Lurie Cancer Center of Northwestern University, Chicago, IL. The study was approved by the Northwestern University Institutional Review Board on 9/22/22 (IRB #: STU00217727); clinicaltrials.gov listing is pending. Key eligibility criteria: BRAF-mutated, stage IV colon cancer, with at least one line of therapy; ECOG PS 0/1, preserved organ function, and measurable disease at baseline. Key exclusion criteria: prior treatment with BRAF/MEK inhibitors; history of acute/chronic pancreatitis, psoriasis, or porphyria. Patients will receive standard of care encorafenib 300 mg daily and cetuximab IV weekly (panitumumab IV q 2 weeks can be used per investigator discretion). After a 14-day lead-in, HCQ 400 mg BID will be added. Each cycle is 28 days. CT scans will be done every 2 cycles, and blood will be taken every 2 weeks during the first 2 cycles for metabolomics analysis. The trial utilizes a Simon 2-stage admissible design. 14 patients will be enrolled in stage 1; if 4 or more responses are observed, the trial will continue to Stage 2 in which an additional 24 patients will be enrolled for a total sample size of 38 patients. The primary endpoint is objective response rate (ORR). Secondary endpoints are safety/efficacy, progression-free survival, overall survival and duration of response/stable disease. The exploratory endpoint is changes in markers of autophagy over time. The null hypothesis is an ORR of 20% (per the BEACON trial), and the alternative hypothesis is an ORR of 40%. This is the first trial exploring autophagy modulation in advanced, BRAF-mutated colon cancer. This study aims to show that autophagy inhibition with HCQ circumvents acquired resistance to BRAF + EGFR inhibition in advanced colon cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.TPS262
    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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  • 2
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    Clinical, environmental, genetic, and genomic profile of men with early-onset aggressive prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e17049-e17049
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17049-e17049
    Abstract: e17049 Background: Although prostate cancer (PC) is heterogeneous, the rate of patients diagnosed with aggressive metastatic disease at a young age has been increasing. Prior studies defining genetic abnormalities in high-risk PC have not focused on this unique population of patients, thus the clinical and molecular features of these lethal PC phenotypes are not well described. Methods: This multi-institutional study evaluated two cohorts. Cohort 1, reported here, included early-onset (age ≤ 60) PC that was metastatic (N+ or M+) at diagnosis or PC that metastasized within 5 years post curative intent/local therapy. Cohort 2 included men with metastatic hormone sensitive PC who rapidly progressed (≤ 14 months) after systemic therapy. Data was collected to define clinical and genomic profiles, including sequencing of somatic & germline DNA, circulating tumor DNA and tumor RNA. Standard descriptive statistics were used. Results: 44 patients were enrolled. Median age at diagnosis was 55 years (range 41-60); 84% were White and 14% were Black. Median prostate specific antigen at diagnosis was 20 (range 1-534 ng/mL). 54% reported a family history of PC, while breast and colorectal cancer were reported in 35% and 14%, respectively. 4.5% reported a history of biochemical agent exposure. 58.5% of patients had De Novo distant metastatic disease (56% of these were low-volume) and 59.5% had a Gleason score of 9-10. 59% had received prior local therapy. Germline and somatic genetic data are available for 36 patients (4 are pending). The most common somatic mutation was in TP53 (n=15), followed by BRAF (n=14), AR (n=7), ERBB3 & MYC (n=5 each), CDKN2B, HRAS, MUC4, OBSCN & SPOP (n=4 each). Additional unique mutations in over 1,000 genes were also identified. Germline mutations were detected in BRCA2, ATM, ATP7B & FBN1 (n=3 each), RB1, CDH1, MYBPC3, MYH11 & MYH7 (n=2 each). 11 other unique germline mutations were also identified. Germline mutations were identified in genes previously implicated in hereditary PC ( BRCA2, ATM, PALB2, BRIP1 & CHEK2), with an overall germline incidence of 25%. There were also incidental germline mutations in genes related to hereditary cardiac conditions ( MYBPC, MYH11, MYH7), as well as other hereditary cancers ( RB1 and CDH1). Conclusions: This study evaluated specific criteria to define risk factors associated with the development of aggressive PC at a young age. Nearly 90% of these patients had a family history of cancer, with over 50% reporting a family history of PC. Somatic mutations were identified in genes such as TP53 that are frequently associated with aggressive disease. Additionally, there was enrichment for germline mutations associated with PC that exceeded what has previously been reported and enrichment of mutations not commonly included in PC genetic risk panels. Thus, more work is needed to define characteristics of this high-risk population and optimize management.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e17049
    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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    Global line-1 hypomethylation as novel biomarker for cervical cancer in Nigerian women living with HIV.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e17513-e17513
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17513-e17513
    Abstract: e17513 Background: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria. Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value. Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72). Conclusions: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e17513
    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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  • 4
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    A phase II study of sEphB4-HSA in metastatic castration-resistant prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 84-84
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 84-84
    Abstract: 84 Background: Ephrin receptors and their membrane-localized ligands induce bidirectional signaling and facilitate tumor-stroma interactions. Expression of EphB4 is increased in prostate cancer tissue and cell lines and retained in castration resistant states, and can promote cell migration, invasion, and metastases. Blocking the EphB4-EphrinB2 pathway, which can be accomplished by soluble EphB4 conjugated to human serum albumin (sEphB4-HSA), has efficacy in preclinical models of aggressive prostate cancer. A phase I clinical trial of sEphB4-HSA led to response or stable disease in 56% of patients, with no grade 4 or 5 related adverse events, and combination pembrolizumab sEphB4-HSA led to a 52% response rate in EphrinB2 expressing urothelial cancer. We hypothesized that targeting the EphB4-EphrinB2 pathway may serve as a therapeutic target in the treatment of metastatic castration resistant prostate cancer (mCRPC). Methods: We conducted a single arm, phase II trial in patients with progressive mCRPC and treatment with at least one second generation androgen receptor (AR)-targeted therapy but no more than three prior therapies for mCRPC. On Day 1 of each cycle patients received sEphB4-HSA 1000 mg IV, with cycle length 14 days cycles 1-6 and cycle length 21 days for cycle 7 and beyond. The primary endpoint was confirmed prostate specific antigen (PSA) response rate (confirmed decrease in PSA by 〉 50%). We employed a Simon two stage Minimax design, requiring two or more responses among the first 15 patients to enroll an additional ten patients. Results: Fourteen eligible patients enrolled in the study. Median age was 73.5 years (range 52-83), patients had a median baseline PSA value of 65.11 ng/mL (range 7.77-2850 ng/mL) and received a median of three prior therapies (range 1-3) for mCRPC. Ten patients received prior taxane for mCRPC or hormone sensitive prostate cancer. The median length of treatment with sEphB4-HSA was 6.5 weeks (range 2-35 weeks). The potentially treatment-related adverse events (AEs) that occurred in more than 25% of patients were hypertension (10 patients) and fatigue (7 patients). Three patients experienced a serious adverse event potentially related to therapy, including one patient with a grade 5 event (cerebral vascular accident) possibly related to study drug. No patient had a confirmed PSA response, and the study was stopped for futility. Thirteen patients had PSA progression ( 〉 25% increase in PSA), and one patient withdrew due to toxicity prior to having an evaluable PSA response. The median time to PSA progression was 28 days (95% CI 28-64 days), and median time to radiologic progression was 55 days (95% CI 55 days-NR). Of three patients with measurable disease, two had stable disease and one had progressive disease. Conclusions: In patients with mCRPC who progressed on prior second generation AR-targeted therapy, sEphB4-HSA monotherapy had no discernable anti-tumor activity. Clinical trial information: NCT04033432.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.084
    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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  • 5
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    Treatment with pembrolizumab in combination with the oncolytic virus pelareorep promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 4144-4144
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 4144-4144
    Abstract: 4144 Background: Pelareorep is an intravenously delivered oncolytic reovirus that can induce a T-cell-inflamed phenotype in pancreatic ductal adenocarcinoma (PDAC). In prior studies, tumor tissue analysis from patients treated with pelareorep shows pelareorep replication, increased T cell infiltration, and upregulation of PD-L1. We hypothesized that pelareorep in combination with pembrolizumab in patients with PDAC would lead to improved responses and anti-tumor immunological changes within peripheral blood and tumor biopsies in responding patients. Methods: PDAC patients who progressed after first-line treatment received pelareorep at a dose of 4.5x10 10 TCID 50 IV on Days 1, 2, 3 & 8 of Cycle (C) 1, and Days 1 & 8 with C2 onwards. Pembrolizumab was administered on Day 1 of each 21-day cycle at 200 mg IV. The primary objective was overall response rate by RECIST v 1.1 criteria. Secondary objectives included evaluating immunological changes within tumor tissue and peripheral blood, performed by multi-plex immunohistochemistry and spectral flow cytometry (Cytek), respectively. Results: Thirteen patients were enrolled. Disease control was achieved in 33% of the 12 efficacy-evaluable patients. One patient achieved a partial response (PR). Three additional patients achieved stable disease (SD). On-treatment tumor biopsies, collected during C1, showed pelareorep replication, increased infiltration of CD8+ T cells and PD-L1+ cells, and decreased expression of VDAC1, a mitochondrial gatekeeper for tumor promotion, relative to archival tissue. Reduced infiltration of Foxp3+ regulatory T cells (Treg) was observed in patients showing tumor response. Peripheral blood was collected at day 1 of each cycle and on C1 day 8. Relative to pretreatment samples, the number of CD8+ effector memory T cells and B cells tend to increase while the number of Treg cells declined in C2 onwards in patients with tumor response. Furthermore, these patients had increased expression of the mitochondrial protein TOMM20 in CD8+ T cells and decreased expression of PD-1 and the H3K27me3 epigenetic mark in Treg. Treatment was well tolerated with most treatment-related adverse events, including flu-like symptoms, being grade 1 or 2. Conclusions: The combination of pelareorep and pembrolizumab showed a manageable safety profile and modest efficacy in an unselected PDAC population. Additional correlation analyses between treatment efficacy and immunological changes will be presented. The anti-tumor activity of pelareorep and checkpoint blockade therapy is being evaluated further in additional ongoing studies. Clinical trial information: NCT03723915.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.4144
    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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    Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer
    American Society for Clinical Investigation ; 2022
    In:  Journal of Clinical Investigation Vol. 132, No. 14 ( 2022-7-15)
    Details
    In: Journal of Clinical Investigation, American Society for Clinical Investigation, Vol. 132, No. 14 ( 2022-7-15)
    Type of Medium: Online Resource
    ISSN: 1558-8238
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1172/JCI158800
    DOI: 10.1172/JCI158800DS1
    DOI: 10.1172/JCI158800DS2
    DOI: 10.1172/JCI158800DS3
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2022
    detail.hit.zdb_id: 2018375-6
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  • 7
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    Outcomes of Cancer Patients with COVID-19 in a Hospital System in the Chicago Metropolitan Area
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 9 ( 2022-04-28), p. 2209-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 9 ( 2022-04-28), p. 2209-
    Abstract: Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020. Seventy-five (18.0%) patients died due to COVID-related complications. Older age ( 〉 60), male gender, and current treatment with immunotherapy were associated with shorter overall survival. Laboratory findings showed that higher platelet counts, ALC, and hemoglobin were protective against critical illness and death from COVID-19. Conversely, elevated inflammatory markers such as ferritin, d-dimer, procalcitonin, CRP, and LDH led to worse clinical outcomes. Our findings suggest that a thorough clinical and laboratory assessment of infected patients with cancer might help identify a more vulnerable population and implement more aggressive proactive strategies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14092209
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 8
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    BRCAAWAY: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 5018-5018
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5018-5018
    Abstract: 5018 Background: The PARP-inhibitor olaparib is approved for mCRPC patients (pts) with deleterious germline or somatic homologous recombination repair gene mutations (HRRm). PARP1 interacts with androgen signaling, and castration-resistant tumor cells exhibit increased PARP1 activity. Preclinically PARP1-inhibition synergizes with androgen receptor (AR) targeted therapy. BRCAAway is a biomarker selected, randomized, open-label, multicenter phase 2 trial evaluating efficacy of targeting AR vs PARP vs combination in first line mCRPC patients with germline and/or somatic HRRm in BRCA1, BRCA2, or ATM. Methods: Eligible mCRPC pts underwent tumor next generation sequencing and germline testing. Pts with inactivating BRCA1, BRCA2 and/or ATM alterations were randomized 1:1:1 to Arm 1 abiraterone (1000 mg daily) + prednisone (5mg bid) (Abi/pred), Arm 2 olaparib (300 mg bid) or Arm 3 olaparib + Abi/pred. The primary end point is progression-free survival (PFS) analyzed using Kaplan-Meier estimates and Cox regression. Secondary endpoints include measurable disease response rate (RR) by RECIST, PSA-RR, undetectable PSA (≤ 0.2 ng/ml) and toxicity. Arms 1 and 2 pts were allowed to cross over at progression. Pts with other HRRm were treated with olaparib; Arm 4 (ongoing). Results: 161 pts were registered and had NGS testing; 60 pts were randomized to Arms 1-3; to date 59 are evaluable for toxicity and 53 are evaluable for PFS. Baseline median age 67 (range 42-85) years; 54 pts were White, 6 were Black; sites of disease: bone only (n=31), soft tissue only (n=18), bone and soft tissue (n=10); median PSA 14.61 ng/ml (range 0.15-4036.8). Mutational status: BRCA1 only n = 2, BRCA2 only n = 39, ATM only n = 8, and 〉 1 HRRm n = 11. 34 pts had germline and 26 had somatic mutations. Median (range) follow-up time: 8.3 (0.8, 33.3), 12.2 (2.7, 21.8) and 16.8 (2.9, 41.7) months in Arms 1, 2 and 3. 43 pts had treatment-related adverse events; most common were fatigue (23 pts; 1 Grade (G) 3, 22 G1/2), nausea (17 pts, G1/2), and anemia (9 pts, 2 G3, 7 G1/2). ≥50% PSA decline was 79%, 67%, and 85% of pts in Arms 1, 2, and 3, respectively. Median PSA nadir (ng/mL) (95% CI) Arms 1-3: 2.17 (0.44, 49.27), 3.10 (0.83, 12.01), and 0.50 (0.10, 2.13), respectively. Undetectable PSA, median PFS, and 12-month PFS by Arm are listed in the table. Conclusions: In mCRPC pts with inactivating BRCA1, BRCA2 and/or ATM alterations Abi/pred + olaparib was well tolerated and resulted in longer PFS and better PSA response vs either agent alone. Clinical trial information: NCT03012321. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.5018
    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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  • 9
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    Multicenter, open-label phase II study of daily oral regorafenib for chemotherapy-refractory, metastatic and locally advanced angiosarcoma.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 11561-11561
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 11561-11561
    Abstract: 11561 Background: Angiosarcoma has a particularly poor prognosis with 5-year overall survival rates of approximately 30-40%. Treatment of locally advanced and metastatic angiosarcoma is inadequate. Data strongly suggest concurrent, potent inhibition of VEGFR and Tie2 represents an attractive therapeutic strategy in angiosarcoma. Regorafenib displays potent VEGFR and Tie2 receptor inhibition and also possesses activity against additional potential targets in angiosarcoma including PDGFRs, RAF, KIT and FGFR, amongst others. Methods: A multicenter phase II study of regorafenib in patients with locally advanced or metastatic angiosarcoma was conducted through the Midwest Sarcoma Trials Partnership. Adequate performance status, organ function, measurable disease (RECIST 1.1) and 1-4 prior therapies were required. Regorafenib 160 mg PO daily was given in 28-day cycles (21 days on, 7 days off) until disease progression (PD) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), assessed at 16 weeks. Secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), OS, and safety and tolerability. A Simon 2-stage design was used. Results: After final enrollment of the second stage, a total of 31 pts were enrolled at 6 sites, 23 are evaluable for response. Median age was 65 (range 30-91); 50% were female, 67.7% had metastatic disease. PFS at 4 months is 52.2% with a median PFS and OS of 3.55 and 11.4 months. 1 confirmed CR and 2 PR, 12 SD and 8 PD were observed. ORR and CBR are 14.29 and 65.2%, respectively. No uncommon grade 3-4 adverse events were observed. 6 pts were non-evaluable due to refusal of further therapy and 2 patients progressed prior to first evaluation. Conclusions: Regorafenib was well tolerated in this study of pretreated patients with angiosarcomas and met its primary endpoint with a median PFS 〉 45% at 4 months. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were complicated by early withdrawals of patients. RECIST responses were encouraging and regorafenib has a clinically meaningful 4-month PFS. Clinical trial information: NCT02048722 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.11561
    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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  • 10
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    Arm Subscore of Motricity Index to Predict Recovery of Upper Limb Dexterity in Patients With Acute Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  American Journal of Physical Medicine & Rehabilitation Vol. 99, No. 4 ( 2020-4), p. 300-304
    Details
    In: American Journal of Physical Medicine & Rehabilitation, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 4 ( 2020-4), p. 300-304
    Abstract: The aim of this study was to determine whether the arm subscore of the Motricity Index 1 wk after stroke can predict recovery of upper limb function according to the Action Research Arm Test before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up. Design This was a prospective cohort study of patients with acute ischemic stroke admitted to a single acute care hospital and affiliated inpatient rehabilitation facility between 2016 and 2018. Upper limb dexterity of the impaired limb was assessed using the arm subscore of the Motricity Index and Action Research Arm Test. Receiver operating characteristic curve analysis was used to determine optimal cutoffs of the initial arm subscore of the Motricity Index for a good functional outcome defined as Action Research Arm Test score of 45 or higher. Results Ninety-five patients were evaluated at median 6, 26, and 98.5 days after stroke. The median (interquartile range) arm subscore of the Motricity Index at 1 wk was 77 (20.3–93). The median (interquartile range) Action Research Arm Test scores before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 33 (3.5–52) and 52 (34–55.8), respectively. The optimal arm subscore of the Motricity Index to predict Action Research Arm Test score of 45 or higher before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 71 and 58, respectively. Conclusions Early arm subscore of the Motricity Index at 1 wk predicts upper limb functional capacity before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up.
    Type of Medium: Online Resource
    ISSN: 1537-7385 , 0894-9115
    URL: Article
    DOI: 10.1097/PHM.0000000000001326
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2272463-1
    detail.hit.zdb_id: 2049617-5
    SSG: 31
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