tbuckley/cabot-search huggingface dataset:
The course of depression, inflammation in the serum and tumor microenvironment, and survival in the context of advanced cancer.
Authors: Jennifer Lynne Steel, Kevin H Kim, T. Clark Gamblin, Danyelle Fraser, Michelle Biala, Alexandra Savkova, Lisa Butterfield, David A. Geller, J. Wallis Marsh, Allan Tsung
Journal: Journal of Clinical Oncology (2013)

9507 Background: The aims of the present study were to study the course of depression in patients diagnosed with cancer and the link with biomarkers of inflammation in the serum or tumor microenvironment and survival. Methods: A total of 474 patients diagnosed with advanced cancer were administered the Center for Epidemiological Studies-Depression (CES-D) scale every 2-months and blood samples were drawn to assess biomarkers of inflammation in the serum and tumor microenvironment. The course of depression was estimated using a semi-parametric trajectory analyses and cross-lagged panel analyses were performed to assess the link between depression and biomarkers of inflammation. Cox regression analysis was use to test the link between depression and survival while adjusting for demographic and disease specific factors. Results: A three-class solution was chosen based on Bayesian information criterion and theory. The first class, “not depressed,” with a mean CES-D score of 6.7 at baseline contained 32% of patients and no significant change in depression scores across time. The second class, “mildly depressed” (53% of sample) had a significant increase in the mean CES-D from 14.5 at baseline to 18.0 at 12 months and 20.0 at 16 months [B = .35, z = 3.12, p = .002]. The third class, “severely depressed,” with a mean of 31.5 at baseline (15% of patients) and no significant change win depression over 24 months. Depression predicted serum levels of Tumor Necrosis Factor (TNF)-alpha and Interleukin-1alpha at subsequent time points and was associated with High Mobility Group Box 1 in the tumor microenvironment. Trajectory group assignment significantly predicted survival after demographic and disease specific factors were adjusted (p=0.04). The non-depressed trajectory group had a median survival of 13 months (95%CI=8.9-17.1), the mildly depressed group median survival was 10 months (95% CI 7.1-12.9) and the severely depressed group median survival was 6 months (95% CI=7.6-12.4). Conclusions: These findings may facilitate the targeting of psychosocial and biological interventions to reduce depression symptoms, improve quality of life, and potentially slow disease progression.
Can average-risk medulloblastoma adult patients be treated with radiotherapy and plus chemotherapy?
Authors: Enrico Franceschi, Alicia Tosoni, Marco Bartolotti, Alexandro Paccapelo, Raffaele Agati, Antonella Bacci, Stefania Bartolini, Rosalba Poggi, Dario Palleschi, Carmelo Sturiale, Antonio Fioravanti, Barbara Masotto, Claudio Ghimenton, Franco Alessandrini, Girolamo Crisi, Alba Ariela Brandes
Journal: Journal of Clinical Oncology (2014)

2022 Background: The standard treatment in children with average-risk medulloblastoma (MB) is chemotherapy after reduced-dose radiotherapy (23.4 Gy of craniospinal irradiation and a posterior fossa boost to 55.8 Gy). However, in adults, there is no agreement on the use of adjuvant chemotherapy in this setting. Methods: We performed a retrospective analysis of adult MB pts with average-risk disease, defined as no postsurgical residual (or <1.5 cm2) and no metastatic disease (M0). Main inclusion criteria were: age > 16 years, post-surgical treatment with standard craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). Results: From 1988 to 2012 were accrued 43 average-risk MB pts treated with surgery and adjuvant radiotherapy. Fifteen (34.9%) pts received also chemotherapy: 7 before radiotherapy (RT), 5 after RT, and 3 before and after RT. Median age was 31 years (range: 16-57), M/F ratio 27 (62.8%)/16 (37.2%). Histology was classic in 24 pts (55.8%), desmoplastic in 12 pts (27.9%), extensive nodularity in 5 pts (11.6%), large cell/anaplastic in 2 pts (4.7%). Reasons to administer chemotherapy were residual disease <1.5 cm in 9 pts (60.0%), delay in RT start in 6 pts (40.0%). After a median follow up time of 10 years (range: 8-13), median overall survival (OS) was 18 years (95%CI: 9 – 28) in pts who receive RT alone, and was not reached in pts treated with radiotherapy plus chemotherapy. The survival rates at 5,10 and 15 years were 100%, 78.6% (95% CI: 60.0-97.2%) and 60.2% (95%CI: 36.9-83.5%), in pts treated with RT alone, and 100%, 100% and 100%, in pts treated with RT plus chemotherapy (p=0.079). To date, all pts receiving adjuvant chemotherapy are alive. Univariate analyses did not show significant differences in survival by gender (P=1.000), age (P=0.070) and T stage (T1-Ta vs T3b-T4, P=0.881) between groups. Conclusions: Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult pts. Due to the extreme rarity of MB in adults, prospective trials remain a challenge. Further improvements might drive to add chemotherapy in average-risk setting with less favorable biological signatures (large cell/anaplastic MB and non-WNT group).
Prognostic factors in malignant ovarian germ cell tumors: The SEER experience 1978-2010.
Authors: Olesya Solheim, David Marc Gershenson, Claes Trope, Erik Rokkones, Charlotte C. Sun, Harald Weedon- Fekjaer, Sophie Fossa
Journal: Journal of Clinical Oncology (2014)

e15534 Background: In patients with malignant ovarian germ cell tumors (MOGCT) to evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD), socioeconomic (SES) and sociodemographic status (civil status, residency) on cause specific survival (CSS). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors. Methods: 2541 patients with MOGCT, reported to the Surveillance, Epidemiology, and End Results program (1978 to 2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI). Results: Five-year CSS was 97.0% (95% CI, 95.8% to 98.2%), and 92.0% (95% CI, 90.6% to 93.4%), respectively for dysgerminoma, and non-dysgerminoma. Increasing age at diagnosis and presence of metastasis were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (HR, 1.59; 95%CI, 1.11 to 2.28) and treatment before 1990 (HR, 2.65; 95%CI, 1.83 to 3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95%CI, 1.17 to 5.25). Second cancer was diagnosed in 10 % of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group (P=.002). Conclusions: Increased attention should be directed toward the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.
Additive/synergistic efficacy of zoledronic acid and LBH589 in the spheroid-based cellular angiogenesis assay
Authors: J. Soltau, H. Weber, C. Schächtele, J. Drevs
Journal: Journal of Clinical Oncology (2009)

e14627 Background: The compounds Zoledronic acid (ZA) and LBH589 (histon deactetylase (HDAC) inhibitor) have shown in previous experiments antitumoral and antiangiogenic effects. Aim of this study was to determine their ability to inhibit VEGF-A induced endothelial cell (EC) sprouting and to observe potential additive/synergistic effects of the combination ZA and LBH589 in the spheroid-based cellular 3D angiogenesis assay. Methods: HUVEC spheroids were embedded in a 3D collagen gel, stimulated with VEGF-A [25 ng/ml] and treated for 24h with different concentrations of ZA alone or in combination with LBH589. Sprouting intensity of EC spheroids was quantitated by an image analysis system determining the cumulative sprout length per spheroid using an inverted microscope and digital imaging software. The mean of the cumulative sprout length of 10 randomly selected spheroids was analyzed as an individual data point. Results: Before testing the compounds in combination the single IC 50 values for ZA (42 μM) and LBH589 (2.9 μM) were determined. The IC 50 of ZA has to be considered with caution because of the low inhibitory effect which did not reach basal sprouting levels. In the first combination experiment a dilution series of ZA was tested in combination with a constant LBH589 concentration [2.9 μM, IC 50 value as determined previously]. The combination of ZA with LBH589 was ∼330 fold more effective in the inhibition of EC sprouting than ZA alone [0.58 μM compared to 190 μM]. However, the sprouting intensity in the combination of LBH589 and ZA was very low. Therefore the experiment was repeated with a dilution series of ZA in combination with a constant LBH589 concentration that showed no inhibition of EC sprouting previously (1 μM). The second combination experiment revealed IC 50 values of 1300 μM for ZA alone and 1.5 μM in combination with LBH589 [1 μM]. The combination LBH589 and ZA is again ∼870 fold more effective in the inhibition of EC sprouting than ZA alone. Conclusions: Our results indicate a very strong synergistic effect of the combination ZA and LBH589 in the spheroid-based angiogenesis assay. No significant financial relationships to disclose.
Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival.
Authors: Ester Simeone, Giusy Gentilcore, Anna Romano, Antonio Daponte, Corrado Caraco, Antonio M Grimaldi, Marcello Curvietto, Assunta Esposito, Paola Queirolo, Nicola Mozzillo, Paolo Antonio Ascierto
Journal: Journal of Clinical Oncology (2012)

8573 Background: Ipilimumab (Ipi) is approved in the US as first and second line therapy in patients with metastatic melanoma (MM) and in MM patients with previous therapy in the EU, based on an overall survival benefit shown in a phase III study (Hodi, NEJM 2010). To date, no clinical parameter has been found to be predictive for response to treatment and only few immunologic changes have been identified as potential candidates. Methods: From June 2010 to November 2011 we treated in the Expanded Access Program with Ipi at 3 mg/kg, 95 pre-treated metastatic melanoma patients. The median age was 58 yrs (range 17-84); 10 pts (10,5%) were stage IIIc inoperable, 2 pts (2,1%) stage M1a, 4 pts (4,2%) stage M1b, and 79 pts (83,2%) stage M1c. 30/95 pts had brain metastases and 1/95 spinal cord metastases. All 95 patients were evaluable for response (DCR = CR+PR+SD according the irRC), overall survival, safety, including changes in LDH, CRP (C-reactive protein) and lymphocyte populations (CD4+,CD4CD25+,FOXP3/T-Reg cells). PBMC and sera were collected at week 0, 4, 7, 10 and 12. Results: We found a statistical significant decrease of LDH, CRP and FOXP3/T-Reg cells (p&lt;0.0001; χ 2 and Mann-Whitney), and an increase of lymphocyte count (p&lt;.0001) in the responders group. These differences were also correlated to survival (log-rank test). No differences were observed for CD4+ and CD4+CD25+ between responders and non-responders (p=0.39;p=0.83; Mann-Whitney). An ORR of 22.1% (1CR+20PR; 95% CI 13.8-30.4) and a DCR at week 24 of 37.9% (36/95; 28.1-47.6, 95% CI) were observed. Median overall survival was estimated of 7.8 months (95%CI:5.0-10.6), with a p value not evaluable at the moment of the analysis due to insufficient follow-up because of long-term survival. Adverse events were registered in 40% (38/95) of patients and the most frequent were of grade 1 and 2 (pruritus 57.9%; rash 5.3%; thyroditis 5.3%). Conclusions: The decrease of LDH, CRP and T-Reg cells during Ipi treatment suggest these parameters should be further explored as potential predictive markers for response and survival. Given the potential clinical utility of these findings, these data warrants further prospective validation in a randomized trial.
Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia
Authors: Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Journal: Blood (2017)
Down-Regulation of Signal Transducer and Activator of Transcription 3 Enhances Acute Myeloid Leukemia-Derived Dendritic Cell Function
Authors: Michael T Brady, Austin Miller, Sheila Sait, Laurie A Ford, Minderman Hans, Eunice S. Wang, Kelvin P Lee, Heinz Baumann, Meir Wetzler
Journal: Blood (2010)
HIV-associated anaplastic large cell lymphoma
Authors: J. Castillo, C. Milani, L. Pantanowitz
Journal: Journal of Clinical Oncology (2009)

e19563 Background: Anaplastic large cell lymphoma (ALCL) is a CD30+ T-cell lymphoma that is generally unrelated to EBV in the non-HIV setting. Based upon anaplastic lymphoma kinase (ALK) expression, the new WHO classification provisionally distinguishes between ALK+ (favorable) and ALK- (unfavorable) ALCL. The characteristics of ALCL, such as ALK expression and EBV coinfection, in individuals with HIV infection have not been adequately evaluated. The aim of this study was to investigate these features in HIV-associated ALCL cases. Methods: A MEDLINE search for all cases of HIV-associated non-cutaneous ALCL was undertaken. Data regarding patient age, gender, HIV status (CD4 count, viral load, opportunistic infections), HAART, lymphoma features (B symptoms, stage, sites of involvement, immunophenotype, ALK expression, molecular studies), EBV coinfection, therapy and outcome (survival, cause of death) were extracted and analyzed. Results: A total of 23 cases were included. Patients were of median age 39 years with a male:female ratio of 7:1. Median CD4+ count was 76 cells/mm3 and HIV viral load 416,500 copies/ml. Most (67%) patients had an opportunistic infection, although only 3 (17%) were on HAART. ALCL was extranodal in 22 cases (96%) affecting most commonly lung, soft tissue and liver. Many (78%) patients had stage IV disease and B symptoms were reported in 9 cases (50%). T-cell receptor gene rearrangement was present in all cases, CD30 was positive in 22 (96%), and the vast majority (90%) were ALK-negative. EBV was identified in 8 (35%) cases. Therapy for ALCL was documented in 15 (67%) cases; 64% received CHOP. In 2 of the 3 patients who were on HAART, long-term survival was achieved. Many (68%) patients died, with a median survival of 9 months. Death was caused by either lymphoma progression (42%) or infection (58%). Conclusions: HIV-associated non-cutaneous ALCL appears to affect younger individuals and is associated with EBV infection in a subset of cases. Apart from marked immunosuppression, the poor prognosis of HIV-associated ALCL appears to be related to the absence of ALK expression, advanced stage at presentation with prominent extranodal disease, inadequate therapy including HAART, and poor response to CHOP. Further research is needed to better understand and treat this unique HIV-associated lymphoma. No significant financial relationships to disclose.
Prognostic significance of preoperative neutrophilia on recurrence-free survival in meningioma
Authors: Shirin Karimi, Manav V Vyas, Lior Gonen, Raha Tabasinejad, Quinn T Ostrom, Jill Barnholtz-Sloan, Suganth Suppiah, Gelareh Zadeh, Kenneth Aldape
Journal: Neuro-Oncology (2017)

Meningioma is the most common primary intracranial tumor and recurrence is one of the important challenges in patient management. Prognostic factors for tumor recurrences in these patients especially before surgical resection are not fully characterized. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in solid malignancies. We aimed to assess the association between hematologic parameters and tumor recurrence in patients with meningioma.Preoperative complete blood count (CBC) data were analyzed in patients with newly diagnosed meningioma (n = 222). Clinical data, including history of corticosteroid therapy, tumor characteristics, and follow-up, were obtained. Recurrence-free survival (RFS) was evaluated using Cox proportional hazards models and log-rank tests.Using preoperative CBC data from patients prior to any steroid therapy, 51 (23%) patients had neutrophilia. In univariate analysis, neutrophilia was significantly associated with meningioma recurrence (hazard ratio [HR] 2.73; P < 0.01). Neither leukocytosis nor lymphocytosis was associated with RFS. In multivariate analysis, after adjusting for tumor grade, tumor size, and extent of resection, neutrophilia remained an independent prognostic factor for RFS (HR 2.23, P = 0.01). Forty-six (21%) patients had low hemoglobin levels indicative of anemia, and the presence of anemia showed a trend toward high risk for recurrence (HR 1.83; P = 0.06).The presence of neutrophilia was associated with higher rate of tumor recurrence in patients with meningioma. Validation of these results and the biologic role of neutrophilic inflammatory/immune reaction in meningioma requires further investigation.
Intraplaque Hemorrhage and Progression of Coronary Atheroma
Authors: Frank D. Kolodgie, Herman K. Gold, Allen P. Burke, David R. Fowler, Howard S. Kruth, Deena K. Weber, Andrew Farb, L.J. Guerrero, Motoya Hayase, Robert Kutys, Jagat Narula, Aloke V. Finn, Renu Virmani
Journal: New England Journal of Medicine (2003)

Intraplaque hemorrhage is common in advanced coronary atherosclerotic lesions. The relation between hemorrhage and the vulnerability of plaque to disruption may involve the accumulation of free cholesterol from erythrocyte membranes.
ICU futility in advanced cancer patients.
Authors: Alva B Weir, Katheryn Ryder, Muthia Muthia, Karen Clark, Harvey B. Niell, Syed Sameer Nasir
Journal: Journal of Clinical Oncology (2014)

e17586 Background: Large data bases have been analyzed to evaluate the number of cancer patients who die in intensive care (ICU) settings. Little information regarding details of care of these (retrospectively) futile efforts have been explored. Methods: We studied 421 charts of patients who died in the ICU at a university affiliated Veteran’s Affairs Medical Center between 10/2005 and 10/2010. We identified 52 patients with advanced, incurable cancer and performed an in depth review of their records. Results: The mean age was 66 with 9 over 80. Mean duration of cancer awareness was 7.3 months with 14 patients aware of their diagnosis < 1 month. Mean survival in ICU was 4.3 days with 25 living one day or less. 26 patients were supported by ventilators. Only 16 patients had documented discussions regarding treatment preferences or advanced directives prior to admission. 29 did have treatment preference discussions in hospital prior to ICU admission in an urgent situation. 6 patients were directly admitted from the emergency center to the ICU and 6 were post procedure ICU admissions. 38 had expected durations of life prior to ICU of 6 months or less. Only 3 had palliative care consults prior to ICU admission. Conclusions: Decision making behind futile ICU admissions for cancer patients is quite variable and complex. A large percentage of our patients make these decisions on an urgent basis and often within a few weeks of their diagnosis. This data suggests that treatment preference decisions, including ICU admissions, should be made in out-patient settings, divorced from urgent decision making. From this data we have developed an EMR template, designed for easily obtainable out-patient treatment preference discussions, which can be accessed by in-patient providers. Outcome measures utilizing this template are ongoing and preliminary findings will be available.
Sjögren's Syndrome
Authors: Clio P. Mavragani, Haralampos M. Moutsopoulos
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Sjögren's syndrome (SS) is a chronic autoimmune disorder that typically affects exocrine glands--mainly labial and lacrimal--leading to complaints of dry mouth and eyes. Given that periepithelial mononuclear cell infiltrates, both in exocrine glands and in other parenchymal organs (kidney, lung, and liver), are the histopathological disease hallmark, the term autoimmune epithelitis has been proposed. B cell hyperactivity is another cardinal SS feature manifested by the presence of autoantibodies and hypergammaglobulinemia, as well as clinical/serological phenotypes mediated by immune complexes, such as peripheral neuropathy, vasculitic lesions, and hypocomplementemia. These have been designated adverse predictors for lymphoma development in approximately 5% to 10% of patients. Activation of the type I interferon/B cell-activating factor axis in SS has recently attracted particular attention. Inappropriate overexpression of endogenous nucleic acids in a genetically susceptible individual might provide a plausible scenario for the immune activation observed in SS.
Incorporating New Systemic Therapies in Kidney Cancer Treatment
Authors: Eric Jonasch
Journal: Journal of the National Comprehensive Cancer Network (2017)

In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
Prospective assessment of renal function using cystatin C and functional MRI in children with newly diagnosed renal tumors.
Authors: Elizabeth Fox, Kate Amodei, Peter Mattei, Thomas Kolon, Ann M Johnson, Kassa Darge, Frank M Balis
Journal: Journal of Clinical Oncology (2014)

10053 Background: Serum creatinine (sCr) is an imprecise renal function marker in children. Serum cystatin C (cysC) is a more sensitive marker to estimate glomerular filtration rate (GFR). Functional MRI (fMRI) measures the contribution of each kidney to overall renal function. Methods: Renal function was serially evaluated in children with renal tumors. sCr, cysC and contrast enhanced fMRI were obtained at baseline and during therapy in children [n=11,median (range) age 3y (0.5-7.8y)] with newly diagnosed renal tumors. Three children had a tumor predisposition syndrome, one had horseshoe kidney. Diagnoses were Wilms tumor [unilateral (n=5), multifocal/bilateral (n=4)] metanephric stromal tumor (n=1) and no tumor (n=1). Therapy included unilateral total nephrectomy (n=5), partial nephrectomy (n=3), bilateral partial nephrectomy (n=2), chemotherapy (n=9), flank/abdomen radiation (n=4). GFR was estimated using the Schwartz formula (GFRCr) and cysC (GFRcycC). Results: At baseline, median (range) GFRCr was 138 (81-198) mL/min/1.73m2 including 3 patients with GFRCr <100 ml/min/1.73m2 and one had progressive acute kidney injury during therapy; GFRcycC was 108 (77-136) mL/min/1.73m2. Pre- vs post-surgery (n=8), median GFRCr was 142 vs 104 mL/min/1.73m2 (P=0.04), GFRcycC was 114 vs 88 mL/min/1.73m2 (P=0.01). At end of therapy, median (range) percent change from baseline in GFRCr was -23% (-64 to +23%), GFRcycC was -25% (-60 to +24%). fMRI analysis was completed in 26/27 scans. Using fMRI, median (range) percent of total renal function contributed by the involved kidney at diagnosis was 35% (23-48%) and the percent change in total parenchymal volume pre- and post-surgery was -50% (-17 to +63%) after unilateral nephrectomy (n=3) and -9% (-40 to +5%) after partial nephrectomy (n=4). Conclusions: Some children with Wilms tumor have decreased GFR at diagnosis. At end of therapy, median decrease in GFR was 25%. GFRcysC may be more sensitive to changes in renal function after complete or partial nephrectomy. fMRI is feasible and quantifies the contribution of tumor-involved kidney to overall renal function. Partial nephrectomy spared 90% of renal parenchymal volume in this small cohort of children.