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  • 1
    In: Cancers, MDPI AG, Vol. 14, No. 1 ( 2021-12-31), p. 186-
    Abstract: Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic responses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p 〈 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p 〈 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p 〈 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 2
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 2 ( 2020-10), p. e000726-
    Abstract: The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received 〉 10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p 〉 0.05). CT for cancer-related indications predicted for shorter PFS (p 〈 0.001) and was associated with refractoriness to ICI (75% vs 33%, p=0.05) compared with cancer-unrelated indications. This is the first study to demonstrate that neither bCT nor cCT influence response and OS following ICI in HCC. Worse outcomes in CT recipients for cancer-related indications appear driven by the poor prognosis associated with symptomatic HCC.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5046-5046
    Abstract: Introduction: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extra-nodal lymphoma which has historically shown to be therapeutically challenging. Currently, the standard treatment remains to be high dose methotrexate (HD-MTX)-based combination chemotherapy with or without whole-brain radiotherapy. The rarity of this disease has precluded large and randomized controlled trials from taking place. In this retrospective study performed at our tertiary care academic medical center, we report our experience and characterize the nature of this disease in our patient population in a predominantly rural area of North Carolina. We demonstrate the reality and challenges of the therapeutic approaches in an attempt to achieve more durable responses and better outcomes with available treatment regimens in our patient population. Methods: After approval from our Institutional Review Board, medical records and pathology data base at our institution were reviewed to identify patients diagnosed with PCNSL between the years of 2004 and 2014. Eleven cases with no radiographic or other evidence of systemic disease who fulfilled the criteria for PCNSL according to the most recent WHO classification were included in the study. Patients' demographics, clinical presentation, radiographic and pathologic findings and treatment details and outcomes were collected and analyzed. Results: The median age at diagnosis was 60. Most patients were Caucasians (90%) with a slight predominance of males (54% males, 45% females). Clinically, most patients presented with neurologic symtpoms and deficits rather than with 'B' symptoms. Radiographically, all patients had supratentorial and multifocal involvement mostly with frontotemporal lesions. The lesions were seen crossing the corpus callosum mimicking glioblastoma multiforme in 4 patients. The pathologic features in all patients were consistent with diffuse large B-cell lymphoma (DLBCL) characterized by a diffuse intraparenchymal growth pattern. At least focal perivascular distribution of tumor cells was present in 3 cases. CD20 expression was present in all cases and 10 of 11 cases were negative for CD10, consistent with non-germinal center (non-GC) phenotype. Most tumors showed a high Ki67 proliferation rate (80-100%). Six of eleven patients had cytological assessment of the cerebrospinal fluid (CSF) at the time of diagnosis. No patients had lymphoma cells in the CSF indicating lack of leptomeningeal involvement. A total of 2 patients received induction chemotherapy based on the CALBG 50202 protocol including HD-MTX, Temozolamide and Rituxumab. Of the remaining 9 patients, 4 received HD-MTX alone, 3 received HD-MTX with concomitant intrathecal cytarabine, 1 received HD-MTX plus rituximab and 1 received Pemetrexed alone. A total of 2 patients received radiation therapy (WBRT). Five patients died of disease with time to death of disease ranging from 1.5 to 8 months. Three patients are alive at months ranging from 8 months to 3.5 years after diagnosis. One patient has been cured of their PCNSL but developed a secondary systemic DLBCL seven years later. The remaining 2 patients were lost to follow up. We were unable to determine any impact of the individual treatment modalities on the overall survival due to the small number of patients in our study. Conclusion: Our patients were predominantly Caucasian with a median age at diagnosis of 60 years. The tumors were exclusively CD20+ DLBCLs with a high Ki67 proliferation rate and a predominantly non-GC phenotype, indicating an aggressive disease pattern. Majority of the patients were unable to complete standard chemotherapy regimens previously described in the literature. Factors contributing to incomplete therapy included age more than 65 and adverse events from chemotherapy including acute kidney failure and neurotoxicity. We conclude that although HD-MTX with or without radiation therapy is the current standard treatment, it is not necessarily feasible nor appropriate in all patient populations. In our population, success was seen in patients who were younger, less than 65 years, in those who received methotrexate doses of 4g/m2 rather than the standard 8g/m2 and those who received Rituximab as part of their regimen. Larger multicenter retrospective studies may provide better insight into finding more optimal treatment regimens. 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: 2015
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 393-393
    Abstract: 393 Background: Atezolizumab plus bevacizumab (A+B) is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). No evidence exists as to its use in routine clinical practice in patients (pts) with impaired liver function. Methods: This retrospective, multi-center observational study was conducted across 7 tertiary academic referral centres and collected 64 HCC pts consecutively treated with A+B. Efficacy outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of A+B commencement and overall response rates (ORR) and disease control rates (DCR) defined by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1). Safety outcomes included treatment-related adverse events (trAEs) graded (G) according to CTCAE v5.0. Results: Of 64 eligible pts, 54 had BCLC C stage HCC (84%), secondary to hepatitis C cirrhosis (n = 24; 37%), hepatitis B (n = 10; 16%), and non-viral etiologies (n = 40; 47%). Liver function was classified as Child-Pugh (CP) A in 46 patients (72%), B7 in 7 (11%), B8 in 8 (12%), and B9 in 3 (5%). Patients were of performance status (PS) ECOG 0 (n = 39; 61%) and 1 (n = 25; 39%). Pre-treatment upper-gastrointestinal endoscopy was performed in 44 patients (69%), with gastro-esophageal varices found in 18 pts (40%) and graded as 1 (n = 12, 27%), 2 (n = 4, 9%) and 3 (n = 2, 4%) respectively. After a median follow-up of 6.8 months (m) (95% confidence interval [CI], 5.5-8.0), median OS (mOS) was 11.7m (95% CI, 6.2-17.3) whereas median progression-free survival (mPFS) was 6.97m (95% CI, 2.9-11.0). ORR and DCR were 26% and 62% respectively. TrAEs of any grade were documented in 43 pts (67%): 12 pts (18%) had trAEs of G≥3: 7 (11%) atezolizumab-related and 5 (8%) bevacizumab-related. Toxicity led to treatment discontinuation in 3 pts (5%). Compared to CP-A, CP-B pts achieved shorter OS (11.7m [95% CI, 10.3-13.2] vs 6.5m (95% CI, 3.5-9.5), p = 0.029) and PFS (9.1m [95% CI, 5.4-12.8] vs 2.3m [95% CI, 1.7-2.9] , p = 0.001) with no differences in ORR nor in DCR. The rate of trAEs did not significantly differ across CP classes. Median OS was significantly longer in patients achieving a radiologic response (12.7m [95% CI, not reached] vs 11.0m [95% CI, 5.5-16.5] , p = 0.04). Presence and grade of varices was not associated to bevacizumab-related trAEs. Conclusions: This study confirms reproducible efficacy and safety of A+B in routine practice. Despite inferior OS and PFS compared to CP-A, A+B was associated with similar tolerability and radiologic response in CP-B patients, warranting prospective evaluation of A+B in this treatment deprived population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    SAGE Publications ; 2010
    In:  American Journal of Hospice and Palliative Medicine® Vol. 27, No. 3 ( 2010-05), p. 215-218
    In: American Journal of Hospice and Palliative Medicine®, SAGE Publications, Vol. 27, No. 3 ( 2010-05), p. 215-218
    Abstract: The authors present a case report of an adult patient with sickle cell disease (SCD), who required frequent hospitalizations for sickle cell vaso-occlusive painful crisis as well as management of complications that resulted from treatment. The patient demonstrated clinical improvement after initiating palliative exchange transfusions of packed red blood cells (PRBCs) once every 4 weeks. They also promptly addressed their physical and psychosocial issues of care. The author described that because the patient was started on chronic exchange transfusions, there was a significant decrease in hospitalizations and emergency department (ED) visits. They saw a major improvement in the quality of life of this patient. The review of medical literature did not reveal any clear-cut guidelines for palliative chronic exchange transfusion for painful vaso-occlusive crisis in adult patients. This case review highlights the usefulness of this palliative model of care. The burden and benefits of chronic exchange transfusion always need to be weighed carefully.
    Type of Medium: Online Resource
    ISSN: 1049-9091 , 1938-2715
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 6
    In: Journal of Hepatology, Elsevier BV, Vol. 73 ( 2020-08), p. S40-S41
    Type of Medium: Online Resource
    ISSN: 0168-8278
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2027112-8
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  • 7
    In: Journal of Hepatology, Elsevier BV, Vol. 77 ( 2022-07), p. S372-S373
    Type of Medium: Online Resource
    ISSN: 0168-8278
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2027112-8
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  • 8
    Online Resource
    Online Resource
    Mary Ann Liebert Inc ; 2009
    In:  Journal of Palliative Medicine Vol. 12, No. 4 ( 2009-04), p. 385-386
    In: Journal of Palliative Medicine, Mary Ann Liebert Inc, Vol. 12, No. 4 ( 2009-04), p. 385-386
    Type of Medium: Online Resource
    ISSN: 1096-6218 , 1557-7740
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2009
    detail.hit.zdb_id: 2030890-5
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  • 9
    Online Resource
    Online Resource
    SAGE Publications ; 2010
    In:  American Journal of Hospice and Palliative Medicine® Vol. 27, No. 5 ( 2010-08), p. 337-341
    In: American Journal of Hospice and Palliative Medicine®, SAGE Publications, Vol. 27, No. 5 ( 2010-08), p. 337-341
    Abstract: The author presents a case report of an elderly patient who was extremely frail and debilitated. The patient was a resident of a skilled care facility because of advanced chronic illnesses that included end-stage Alzheimer, dementia, and Parkinson disease. This patient had acquired multiple stages III to IV pressure ulcers. Aggressive wound care treatment was initiated with partial success, but the patient passed away before the wound could completely heal. Medical literature was reviewed to offer the best possible wound care approach in providing care to patients who are terminally ill without compromising the patient’s dignity and comfort and at the same time delivering cost-effective quality care.
    Type of Medium: Online Resource
    ISSN: 1049-9091 , 1938-2715
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2236674-X
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  • 10
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-10), p. 1862-
    Abstract: Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p 〈 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57–0.74) versus 0.63 (95% CI 0.54–0.72). ALBI grade at ICI cessation independently predicted for PIOS (p 〈 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p 〉 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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