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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  Annals of Surgical Oncology Vol. 25, No. 12 ( 2018-11), p. 3613-3620
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 25, No. 12 ( 2018-11), p. 3613-3620
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2074021-9
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e16088-e16088
    Abstract: e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C 〉 G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 3
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 12 ( 2019-12-01), p. 6193-6200
    Abstract: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti–PD-1 nivolumab. Objective The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. Design Single-arm, multicenter, phase 2 clinical trial with two-stage design. Setting Comprehensive cancer center. Patients Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. Intervention Nivolumab (240 mg) IV every 2 weeks. Results Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. Conclusion Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
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    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
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  • 4
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1752-1752
    Abstract: Bone marrow examination is an essential and commonly performed bedside procedure in diagnosis and staging of hematological malignancies and benign hematological disorders. Although when performed on the posterior superior iliac spine(PSIS), it is considered a safe procedure with minimal complications, cases of excessive bleeding , hematoma formation, injury to neurovascular structures, retroperitoneal and intraperitoneal hemorrhage, pseudo aneurysm formation and gluteal compartment syndrome have been reported. Cases of retroperitoneal hemorrhage are presumed to occur due to penetration of the needle through the iliac crest indicating that accurate placement and angulation of the biopsy needle is critical to avoid iatrogenic complications. Bone marrow biopsy has been described in various publications and text books. However, standardized technique for positioning the biopsy needle and its penetration orientation are lacking. Various authors have described the correct needle placement and orientation as perpendicular to the bone or pointing towards the anterior superior iliac spine (ASIS) but most of the studies do not specify angulation of the needle. These methods appear to be extrapolated from personal experience and, to date, an evidence based approach for needle angulation has not been described. We present a comparison of different described approaches to perform bone marrow biopsy relative to injury to critical structures should the needle penetrate the inner bone cortex. This study compares the two most commonly used PSIS biopsy approaches that advance the needle towards: 1. The Umbilicus (Medial Approach) 2. Ipsilateral ASIS (Lateral Approach). Methods The study was done on cadavers in the dissection laboratory at the Albert Einstein College of Medicine. The procedure was performed by Attendings and Fellows in Hematology Division who are experienced in performing bone marrow biopsy. Manual Jamshidi needles or powered bone marrow device were used. Anatomy professors helped identify the landmarks and performed dissections after biopsy procedures. The Radiology Department assisted with performing and reading the CT scans of the pelvises. The first phase of study involved placing two dissected cadavers with intact pelvises in prone and lateral positions. Bone marrow needle was placed perpendicular to the PSIS and, during penetration, the direction was changed toward the umbilicus for the Medial Approach and towards the ASIS during the Lateral Approach. A bone marrow biopsy was obtained. Subsequently, using the same needle track, the needle was deliberately pushed through the inner ilial cortex to assess the resultant potential for injury. Keeping the needles in situ, metal wire probes were inserted via the needle for better visualization. The cadavers were further dissected to identify injury to neurovascular bundles and adjacent structures. In the second phase, bone marrow biopsy was performed on two intact cadavers. The needles with inserted probes were left in situ to mark different angulations. The cadavers were then scanned and dissected to identify penetrated structures and closely related neurovascular bundles that were at risk had the orientation varied slightly. Results Dissections and CT scan imaging showed that Lateral Approach was less likely to cause injury to significant neurovascular structures and penetrate the sacroiliac joint in comparison to the Medial Approach. Using the Medial Approach, in the event of penetration of inner cortex, we documented injury to the sacro-iliac joint, femoral nerve, common iliac vessels and mesentery of the sigmoid colon. The needle was observed in close proximity to the iliolumbar vein and artery and the lumbosacral trunk. Using the Lateral Approach, the structures adjacent to the needle were limited to the iliacus muscle and the lateral cutaneous branch of femoral nerve. The lateral approach had the added benefit of more consistent orientation since the relationship of the ASIS to the PSIS is both consistent and palpable whereas the location of the umbilicus may vary. We suggest that the safest way to perform a bone marrow biopsy is to advance the needle in a perpendicular direction to reach the PSIS. Once the needle penetrates the outer cortex of the bone, the direction should be changed pointing towards the ipsilateral ASIS. We believe that this procedure will obviate complications reported in the literature. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4020-4020
    Abstract: 4020 Background: High grade (G3) GEPNENs are a rare and heterogeneous disease entity for which there is little prospective treatment data. EP chemotherapy is the treatment standard but this may not be appropriate for all G3 GEPNEN pts. CAPTEM has demonstrated activity in G3 GEPNENs and may be a promising alternative. EA2142 aimed to determine if CAPTEM was superior to EP in pts with G3 GEPNENs. Methods: This was a multicenter, randomized (1:1) phase II trial for pts with a locally advanced and unresectable or metastatic well differentiated G3 neuroendocrine tumor (NET) or a poorly differentiated, non-small cell G3 neuroendocrine carcinoma (NEC) of suspected gastrointestinal origin and an ECOG PS of 0-2. Pathology must have demonstrated a Ki-67 of 20-100% or at least 10 mitoses/10 high powered field. Pts were randomized to receive capecitabine 750 mg/m2 orally every 12 hours on days 1-14 and temozolomide 200 mg/m2 orally once daily on days 10-14 of a 28-day treatment cycle (Arm A) or etoposide 100 mg/m2 daily on days 1-3 with either cisplatin 25 mg/m2 daily on days 1-3 or carboplatin AUC 5 on day 1 of a 21-day treatment cycle (Arm B). Restaging scans were performed every 8 weeks and toxicity monitored per CTCAEv4. Final statistical plan was to accrue 80 pts to detect a 67% improvement in progression free survival (PFS) (primary endpoint) with CAPTEM as compared to EP, 80% power and one-sided significance level of 0.10. A planned interim analysis for efficacy and futility was conducted. Results: A total of 67 pts were enrolled (Arm A, n=32; Arm B, n=35). Male 58%, African American 4%, Asian 3%. Mean age 61. Among 63 eligible pts, primary tumor site pancreatic 56%, non-pancreatic 43%. Poorly differentiated 57%, well differentiated 33%, unknown 10%. Mean Ki-67 48% (Arm A), 60% (Arm B). The study was closed prior to full accrual due to futility at 57.7% information time. In the interim analysis, among 62 eligible pts, PFS, overall survival and response rate with CAPTEM were 2.43 months (mos) (95% CI 2.04, 7.72), 12.6 mos, 9% respectively vs 5.36 mos (95% CI 2.14, 7.23), 13.6 mos and 10% with EP. Toxicity was evaluable in 57 pts with Grade (G) 3/4 events occurring in 29% of pts on Arm A, 66% of pts on Arm B. G3/4 events occurring in more than 5% of pts on Arm A—febrile neutropenia (n=2); abdominal pain (n=2); diarrhea (n=2); nausea (n=2); neutropenia (n=2); dehydration (n=2) and on Arm B—anemia (n=8); febrile neutropenia (n=2); fatigue (n=2); lymphopenia (n=2); neutropenia (n=12); thrombocytopenia (n=4); leukopenia (n=6). There was one G5 event on Arm A due to sepsis. Conclusions: CAPTEM does not appear to be superior to EP chemotherapy as front-line treatment for pts with G3 NENs but does demonstrate a more favorable toxicity profile. Studies assessing G3 NET independently of G3 NEC are needed. Clinical trial information: NCT02595424.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 6022-6022
    Abstract: 6022 Background: BRAF mutations are present in ~44% of papillary thyroid carcinoma (PTC) and its role in development of PTC is well established. We hypothesized that dabrafenib (BRAF inhibitor) would have efficacy in BRAF mutated PTC and that combining it with trametinib (MEK inhibitor) would result in greater clinical efficacy than dabrafenib alone, through vertical inhibition of the RAF/MAP/ERK pathway and mitigation of potential mechanisms of resistance. Methods: Patients (pts) with BRAF mutated radioiodine refractory PTC who had evidence of disease progression within 13 months prior were randomized to Arm A (dabrafenib 150 mg PO BID) or Arm B (dabrafenib 150 mg PO BID + trametinib 2 mg PO qd). Cross-over to Arm B was allowed at time of progression. Responses were assessed by modified RECISTv1.1 every 2 months. Primary endpoint was objective response rate (ORR) (complete-, partial- and minor-response). With assumed true ORR of 15% vs 35%; and 90% power to identify the correct regimen as most promising, 26 pts were to be accrued in each Arm. Results: In this randomized phase 2 trial, 53 pts (median age 63 years, 38 females) were enrolled; 25% of pts had 1-3 prior therapy with multi-kinase inhibitors. Median follow up was 13 months. Preliminary efficacy results are outlined in Table. The treatment-related adverse events were similar to previously reported phase III clinical trial of these drugs in melanoma. Conclusions: Single agent dabrafenib, as well as combination of dabrafenib/trametinib are well tolerated therapies that result in similar high objective response rates with durable responses in pts with progressive BRAF-mutated PTC. BRAF-pathway targeted therapies provide novel treatment options. Clinical trial information: NCT01723202. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  European Journal of Preventive Cardiology Vol. 30, No. 13 ( 2023-09-20), p. 1323-1324
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 30, No. 13 ( 2023-09-20), p. 1323-1324
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2646239-4
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Heart Failure Clinics Vol. 14, No. 4 ( 2018-10), p. 553-567
    In: Heart Failure Clinics, Elsevier BV, Vol. 14, No. 4 ( 2018-10), p. 553-567
    Type of Medium: Online Resource
    ISSN: 1551-7136
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 9
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 61 ( 2017-11-28), p. 104046-104056
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 10
    In: Cancer, Wiley, Vol. 126, No. 16 ( 2020-08-15), p. 3689-3697
    Abstract: Angiogenesis and fibroblast proliferation are important disease drivers in nonpancreatic neuroendocrine tumors. Nintedanib, an inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor, has activity in nonpancreatic neuroendocrine tumors, and baseline serotonin, which is known to drive fibroblast proliferation through fibroblast growth factor receptor, has a strong, positive correlation with activated but exhausted T cells.
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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    detail.hit.zdb_id: 2599218-1
    detail.hit.zdb_id: 2594979-2
    detail.hit.zdb_id: 1429-1
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