tbuckley/cabot-search huggingface dataset:
Adaptive Immune Gene Signatures Correlate with Response to Flotetuzumab, a CD123 × CD3 Bispecific Dart® Molecule, in Patients with Relapsed/Refractory Acute Myeloid Leukemia
Authors: Sergio Rutella, Sarah E. Church, Jayakumar Vadakekolathu, Elena Viboch, Amy H Sullivan, Tressa Hood, Sarah E. Warren, Alessandra Cesano, Ross La Motte-Mohs, John Muth, Helene Lelièvre, Bob Lowenberg, John F. DiPersio, Jan K Davidson-Moncada
Journal: Blood (2018)
Clinical significance of serum caveolin-1 levels in melanoma.
Authors: Didem Tastekin, Senem Karabulut, Derya Duranyildiz, Faruk Tas
Journal: Journal of Clinical Oncology (2014)

e20049 Background: Caveolin-1 plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of caveolin-1 in melanoma patients. Methods: A total of 60 patients with a pathologically confirmed diagnosis of melanoma were enrolled into this study. Serum caveolin-1 concentrations were determined by the solid-phase sandwich ELISA method. Age and sex matched 30 healthy controls were included in the analysis. Results: The median age at diagnosis was 53,5 years, range 16 to 88 years. The baseline serum caveolin-1 levels of the melanoma patients were significantly higher than in those in the control group (0.47 v 0.37 ng/mL, respectively, p=0.05). Known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, serum LDH levels, and response to chemotherapy were not found to be correlated with serum caveolin-1 concentrations (p>0.05). Moreover, serum caveolin-1 concentration was found no prognostic role on survival (p=0.44). Conclusions: Serum levels of caveolin-1 were a diagnostic marker in melanoma patients. However, its predictive and prognostic value was not determined.
Role of radiofrequency ablation in the treatment of liver metastases from colorectal cancer: Pooled analysis of randomized clinical trials.
Authors: Fabrizio Drudi, Emiliano Tamburini, Manuela Fantini, Antonio Polselli, Lucia Stocchi, Stefania Nicoletti, Barbara Poggi, Luigi Veneroni, Lorenzo Gianni, Davide Tassinari
Journal: Journal of Clinical Oncology (2014)

e14557 Background: To assess the role of radiofrequency ablation (RFA) or hepatic resection (HR) in the treatment of potentially resectable liver metastases from colorectal cancer. Methods: A systematic review of literature in the MEDLINE and EMBASE databases from 1966 to 2013 was independently performed by two authors (DT and FD) All the randomized phase III trials comparing RFA with HR in the treatment of liver metastases from colorectal cancer were considered eligible and included into the pooled analysis. Five-years survival rate was the primary end point of the trial, three-years, and one-year survival rate were the secondary ones. Primary and secondary end points were assessed as death risk reduction (DRR). Heterogeneity between the trials was analysed using the I2 test; the outcome analysis was performed using a random effects model with an alpha error of 5%. The quality of the selected trials was assessed using the Jadad score. Results: Three trials met the selection criteria and were included into the pooled analysis. The outcome of 472 patients included into the three trials were analyzed. There were 107 patients treated with RFA and 365 with HR. HR, in comparison with RFA reduced the three- and five-years risk of death respectively of 24% (p=0.002) and 22.9% (p=0.003), while no differences were observed for one-year DRR (-1.5%, p=0.807). The quality of all the selected trials was low or very low using the Jadad score. Conclusions: Our data seem to confirm that RFA are inferior and should not be considered an alternative to HR in the treatment of potentially resectable liver metastases from colorectal cancer. Further trials, better designed and conducted are probably needed to better define the role of RFA in the treatment of liver metastases from colorectal cancer. Supported by Istituto Oncologico Romagnolo.
The impact of race and socioeconomic status on survival in multiple myeloma.
Authors: Mark A Fiala, Joseph D Finney, Jingxia Liu, Keith Stockerl-Goldstein, Michael H. Tomasson, Ravi Vij, Tanya Marya Wildes
Journal: Journal of Clinical Oncology (2014)

e17554 Background: Advances in multiple myeloma (MM) therapies have improved overall survival (OS), however, not all population subgroups have benefited equally from these advances. Population-based studies suggest that black patients (pts) with MM have a much higher mortality rate than white pts, however, in several studies, after controlling for treatment, OS was similar or superior for black pts. This discrepancy suggests that the poorer outcomes observed in black pts are attributable to factors other than race, such as socioeconomic status (SES). Methods: We performed retrospective chart review of 652 consecutive patients with a diagnosis of MM seen at the Siteman Cancer Center/Washington University School of Medicine from 2000 to 2009. Patients were eligible for analysis if their home address within 6 months of diagnosis was available. SES was approximated by median household income of each patient’s census tract from the American Community Survey (2012 5-year estimates). Comorbidities were categorized with the ACE-27. Results: 562 patients were eligible for analysis. The median age at diagnosis was 59 years (range 33-91); 55% were male; 26% were black. The median household income was $49,464.5 (range 11,917-163,958). The median follow-up was 49 months (range 0-165). Patients in the highest SES tertile (≥ $57,177 median household income) had a median OS of 62.8 months (mos) (95% CI 43.1-82.6 mos), compared to 53.7 mos (45.2-62.3 mos) and 48.6 mos (40.4-56.8 mos) for the middle and lowest tertiles, respectively (p =0.015). They were also less likely to have comorbidities at diagnosis (58% compared to 72% and 76%, p =0.007). Although black pts were more likely to be in in the lowest or middle tertiles than white pts (90% compared to 60%, p <0.001), OS and the prevalence of comorbidities were similar between the two groups. After controlling for severity of comorbidities, age, and race, SES was associated with OS [HR 0.84 (95% CI 0.65-1.10) for middle SES relative to lowest; HR 0.6 (95% CI 0.46-0.83) for highest SES relative to lowest]. Conclusions: Lower SES independently predicts poorer survival. Future studies will examine whether differences in MM disease markers at diagnosis or treatment account for this disparity.
Distribution regularity of anxiety scores in adults.
Authors: Mikhail Blank, Olga Blank, Ekaterina Myasnikova
Journal: Journal of Clinical Oncology (2014)

e20579 Background: Anxiety is one of the principal indices that reflects the human psychological state. The patient’s psychological condition figures in a certain way among the factors influencing the efficiency of cancer patient treatment. Methods: The research material consisted of the data collected during the computer-assisted anxiety survey from the groups suitable for solving the problems, namely: 1) adults with no appreciable disease (103 studies); 2) pregnant women (196 studies); 3) patients with different sites of malignant tumours (39 studies) undergoing the specific treatment; 4) cancer patients (79 studies) brought into lasting clinical remission. All the test subjects had undergone the testing for which the computer-assisted adult version of the Integrative anxiety test (ITT) was used. The test was developed in the V.M. Bekhterev Psychoneurological Research Institute. The computations were performed by the use of Statistica 6.0 package and dip.test function of R.3.00 package. Results: The pairwise comparison of the four groups using the Kolmogorov-Smirnov test shows the significant (p<0.05) difference between the state anxiety scores in the third group and those in the other groups. The rest of the groups have no significant differences between each other (p>0.1 for all pairwise comparisons). In addition, the distribution of scores was tested for unimodality using the Hartigan’s DIP-test. The hypothesis of unimodality was rejected at the p< 10-7level of significance for all the groups except the third one. The p-value for the third group is equal to 0.28 that significantly evidences the unimodality of the score distribution. Thus, the distribution of both state and trait anxiety scores in all the examined groups exhibits bimodality and therefore does not conform with the Gaussian distribution law. Conclusions: We have ascertained that a pronounced unimodal distribution pattern can be only observed for the state anxiety scores in the group of cancer patients undergoing treatment, while this kind of pattern is not revealed in the group of patients brought into the lasting remission. The phenomenon we have discovered is unexpected since it contradicts the prevalent idea of the increase of anxiety in cancer patients.
Results from an institutional universal reflex testing program for MSI/MMR in colorectal cancer.
Authors: Aaron J Franke, Maira Gaffar, Michael Feely, Jason Scott Starr, Hiral D. Parekh, Sanda Tan, Atif Iqbal, Carmen Joseph Allegra, Thomas J. George
Journal: Journal of Clinical Oncology (2018)

796 Background: In colorectal cancer (CRC), clinical guidelines and immunotherapy treatment selection requires knowledge of tumor DNA mismatch repair gene deficiencies (dMMR) or accumulation of microsatellite repeats through genomic errors (MSI-H). Tumors harboring dMMR/MSI-H are found in 15- 20% of early stage CRC while the prevalence is ~5% in metastatic disease. Reflex testing of CRC to identify these important subsets has been proposed as a system-solution to improve identification. We present a large, single-institutional database of CRC reflexively profiled for MSI/MMR status at the University of Florida (UF). Methods: Beginning in 2009, stage IV CRC underwent reflex testing for MSI/MMR status. Earlier stage CRC testing began in subsequent years. For all new CRC diagnosed at UF, concurrent testing for dMMR by IHC (MLH1, PMS2, MSH2, MSH6), MSI by PCR (Promega MSI kit) and NGS is performed with appropriate positive and negative controls. IHC protein loss is confirmed by second GI pathologist. MSI is not performed if inadequate adjacent normal tissue. We conducted a retrospective analysis of all CRC samples analyzed between 2009 and 2017. Clinical data was collected from the EMR. This study was approved by the UF IRB. Results: A total of 388 new CRC cases were reflex tested (16% Stage I, 23% Stage II, 35% Stage III, and 25% Stage IV). Median age at diagnosis was 63 yrs (range: 17-98 yrs), 51% male and 79% white. Both MMR and MSI were performed in 244 (63%) tumors with 100% concordance when concurrently tested. dMMR/MSI-H incidence (20% in overall population) decreased with stage: I/II (31%), III (18%) and IV (~9%) and was associated with BRAF V600E mut in 36/76 cases (47%). Importantly, in pts &lt; 50 yrs, 13% of stage IV patients were dMMR/MSI-H. Conclusions: Reflex testing of MMR/MSI status in CRC is feasible with concordant results. Routine testing results in identification of dMMR/MSI-H at or higher than published rates. Notable findings include the high prevalence in those with sporadic CRC and/or younger than 50 yrs. Continued impact analysis of this approach is warranted to maximize IO therapy offering.
Use of topical corticosteroids among Danish patients with psoriasis
Authors: M.T. Svendsen, M.S. Ernst, K.E. Andersen, F. Andersen, H. Johannessen, A. Pottegård
Journal: British Journal of Dermatology (2019)

Psoriasis is a common chronic inflammatory skin disease, affecting about 2‐4% of the population in Europe. Psoriasis negatively affects patients’ quality of life and is linked to several psoriasis‐associated comorbidities (diseases that occur alongside psoriasis). Topical drugs, which means they are applied directly to the skin, are a recommended first‐line treatment for mild‐to‐moderate psoriasis, but their reported real‐life use is conflicting. This study investigated psoriasis patients’ real‐life use of topical drugs and other antipsoriatic treatments. Danish researchers conducted a drug utilization study based on the nationwide Danish health registry data, including data on all patients above 18 years of age who received a first‐time hospital diagnosis of psoriasis and were prescribed at least one topical drug in the period 2005‐2015 (7,743 patients). The patients were followed for a three‐year period after the time of diagnosis. Among many findings, the authors reported that the most frequently used topical antipsoriatic drugs were combinations containing corticosteroid with calcipotriol, accounting for 31% of the total use. Patients’ use of topical drugs increased around the time of hospital diagnosis. The use also varied considerably between geographical regions as well as for the individual patients, with 25% of the patients using 70% of the total amount of topical treatment. The total use of topical antipsoriatic drugs decreased by 19% during the study period, while use of a drug called methotrexate which is taken by tablet or injection, increased by 70%. The authors concluded that the use of topical antipsoriatic drugs shows considerable diversity over time, regional practices and differences between patients.
Differential expression of STAT1 and STAT3 in peritoneal and tumor-associated macrophages from mice bearing advanced tumors contribute to their diverse immunosuppressive properties
Authors: Marta Torroella-Kouri, Dayron Rodriguez, Yoslayma Cardentey, Risset Silvera, Diana Lopez
Journal: Cancer Research (2008)

250  During cancer progression, a suppressive immune response occurs in the tumor microenvironment, mainly due to the presence of immature myeloid cells and macrophages. Although there is no strong evidence in favor of a decreased systemic immune response until terminal phases of the disease, there are some indications that at locations distant from the tumor, immune cells may already be semi polarized in their degrees of immune proficiency. We have previously shown that thioglycollate-elicited macrophages from mice bearing advanced D1-DMBA3 mammary tumors (T-PEMs) are profoundly dysfunctional, expressing decreased levels of IL-12 and nitric oxide. We have also demonstrated that this impairment is associated with decreased expression and nuclear translocation of NFkB in these cells, providing evidence for a certain degree of immune deficiency in locations distant from advanced tumors. Moreover, NFkB has been shown by several investigators to be constitutively activated in tumor cells and in myeloid cells from tumor hosts, contributing to the inflammatory activity associated with initial stages of tumorigenesis. Transcription factor STAT3 has also been found to be constitutively activated in tumor cells. STAT (signal transducers and activators of transcription) signaling pathways were originally discovered in the context of normal cytokine signaling. STAT1 is obligatory for interferon (IFN) signaling, whereas STAT3 is inducible by IL-6 signaling. Increased STAT3 activity in tumor cells and in tumor-associated cells negatively influences the expression of immune-stimulating molecules. In contrast, IFN-mediated activation of STAT1 is required to mediate an antitumor immune response, and the important role of STAT1 in the regulation of iNOS activity has also been clearly demonstrated. Interestingly, increased levels of STAT3 but undetectable STAT1 activity in myeloid cells from the spleens of tumor bearing mice has been previously reported, but opposite results have been detected in tumor-associated macrophages (TAM) by the same authors. We have recently shown that whereas TAM from D1-DMBA3 bearing mice behave as M2 macrophages, T-PEM are in a M1/M2 interface, already showing some degree of immune suppression. Furthermore, we found that these T-PEM consistently exhibit decreased expression of STAT1 and phospho STAT1 but variable levels of STAT3 and phospho STAT3, whereas TAM show decreased function of NFkB with increased levels of both STAT1/phospho STAT1 and STAT3/phospho STAT3. We believe that our results provide evidence for the existence of different levels of immune suppression in the tumor microenvironment and the periphery of tumor hosts.
Peripheral T-cell lymphomas (PTCL) in the modern era: Prognosis and impact of therapy in a large U.S. multicenter cohort.
Authors: Jeremy S. Abramson, Tatyana Feldman, Aimee Kroll, Lori S. Muffly, Eric S. Winer, Christopher Flowers, Frederick Lansigan, Chadi Nabhan, Rajneesh Nath, Jorge J. Castillo, Andre Goy, Bruce Woda, Steven T. Rosen, Sonali M. Smith, Andrew M. Evens
Journal: Journal of Clinical Oncology (2014)

e19561 Background: PTCLs are a heterogeneous group of diseases with a generally poor prognosis. Optimal initial therapy and the role of stem cell transplantation (SCT) remain controversial. Additionally, more data is needed to refine prognostication in the modern era. Methods: We examined patient (pt) characteristics, treatment and outcome in 341 newly diagnosed PTCL pts from 9 US centers from 2000-2011. Results: PTCL subtypes included PTCL-NOS (31%), ALCL (26%), AITL (23%), NKTCL (7%), ATLL (6%) and other (7%). Median age was 62 yrs (18-95), 74% stage III-IV, 29% bone marrow involved, 49% other EN sites, and 55% elevated LDH. IPI and PIT scores were high risk in 41% and 24% of pts, respectively. 23 (7%) pts received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (76%, 13% with etoposide), hyperCVAD/MA (7%), or other (16%). 36 pts (11%) underwent SCT in 1st remission (85% autologous). Overall response rate to initial therapy was 73% (61% complete); 24% had primary refractory disease. With 39 months median follow-up, 3-year PFS and OS were 32% and 52%, respectively. On univariate analysis for PFS, improved outcomes were noted for ALK+ ALCL, NKTCL, stage I-II, and normal LDH. Univariate analysis of treatment factors found no benefit for etoposide, but identified improved PFS with XRT or SCT in 1st remission. Univariate analysis showed improved OS for ALCL (ALK+ and ALK-), AITL, stage I-II, XRT, consolidative SCT, and normal LDH. On multivariable analysis, however, only stage I-II retained prognostic significance (PFS: HR 0.54 (95% CI 0.34-0.85), P=0.007; OS: HR 0.42 (95% CI 0.22-0.78), P=0.006). Notably, the impact of XRT and SCT in 1st remission was no longer seen after adjusting for stage and initial treatment response. Finally, the most dominant factor predicting outcome was response to initial therapy (CR vs PR/SD/PD), including after adjustment for stage and SCT (PFS HR 0.19 (95% CI 0.14-0.28), P<0.0001; OS HR 0.26 (95% CI 0.17-0.40), P<0.0001). Conclusions: This analysis identified early stage disease and initial response as the dominant prognostic factors. The optimal induction regimen for PTCL pts remains uncertain and our analysis found no clear benefit for consolidative SCT.
Single-cell RNA-Seq of follicular lymphoma reveals malignant B-cell types and coexpression of T-cell immune checkpoints
Authors: Noemi Andor, Erin F. Simonds, Debra K. Czerwinski, Jiamin Chen, Susan M. Grimes, Christina Wood-Bouwens, Grace X. Y. Zheng, Matthew A. Kubit, Stephanie Greer, William A. Weiss, Ronald Levy, Hanlee P. Ji
Journal: Blood (2018)
BET Inhibitors Potentiate Activation of p53 and Killing of AML By MDM2 Inhibitors — a Candidate Combination Therapy
Authors: Peter D Adams, Anne Louise Latif, Ashley Newcombe, Neil Robertson, Maria Terradas, Helen Stewart, Claire Reid, Loveena Rishi Delori, Timothy Chevassut, Xu Huang, Karen Keeshan, Karen Blyth, Mhairi Copland
Journal: Blood (2018)
Limited-stage small cell lung cancer treated with cisplatin/irinotecan and concurrent thoracic radiation therapy.
Authors: Salini Sathya Naidu, Paul R. Walker, Teresa Parent, Maria Eugenia Picton
Journal: Journal of Clinical Oncology (2014)

7598 Background: Concurrent chemotherapy and radiation therapy (CRT) is a curative option for limited-stage small cell lung cancer (SCLC). The standard of care in the United States is concurrent etoposide-platinum CRT. In Asia, CRT with irinotecan and cisplatin has been shown to be an effective and tolerable regimen. (Han et al J Clin Oncol 2005 and Jeong et al Lung Cancer 2006) Irinotecan is a potent radiosensitizing agent (Tamura et al Jpn J Cancer Res 1997). Patients with limited-stage SCLC treated with irinotecan-platinum concurrent CRT were identified from our institutional thoracic oncology program database. Methods: 36 patients with limited stage SCLC from 2006-2013 were identified from our database. Ages 49-85. 17 females and 27 males. All patients were treated with cisplatin 30mg/m2 and irinotecan 65mg/m2 on day 1 and 8 every 21 days for a total of 4 cycles, along with concurrent radiation therapy commensurate with cycle 2. 29 patients received BID concurrent radiation therapy (45Gy), and 7 patients received daily dosing (54Gy). 25 patients received prophylactic cranial irradiation. Median follow-up two years; 22 patients followed for over 3 years. Results: Overall radiographic response rate 67% (18 CR, 8 PR). Median overall survival 19 months. 1 year survival 60%: 2 year survival 44%; 3 year survival 30%. No symptomatic pneumonitis with 13% of patients developing symptomatic esophagitis. Conclusions: Irinotecan and cisplatin with concurrent CRT achieved a 30% 3-year overall survival in an American patient population with limited stage SCLC.
Sentinel lymph node identification using a magnetic tracer for endometrial cancer: A pilot study.
Authors: Jakub Krzysztof Rzepka, Marcin Misiek, Kamil Zalewski, Agnieszka Wrona-Cyranowska, Stanislaw Gozdz
Journal: Journal of Clinical Oncology (2014)

e16550 Background: Traditional techniques of sentinel lymph node (SLN) mapping for endometrial cancer present challenges. The magnetic technique does not use radiation and provides both a color change (brown dye) and a handheld probe for node localization. We performed a pilot study to identify pelvic and para-aortic sentinel lymph nodes with magnetic tracer after cervical injection. Methods: Twelve subjects with early stage endometrial cancer who were scheduled for pelvic lymphadenectomy were prospectively enrolled for SLN mapping. Magnetic tracer (Sienna+) was injected into the cervical stroma at 3 o'clock and 9 o'clock Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared to the non-sentinel lymph nodes. Results: Twelve subjects received cervical injection with at least one SLN observed in all cases. Total number of 31 SLN was identified. All the subjects who received Sienna+ injections mapped a SLN for an observed detection rate of 100%. A median of 2.58 SLN's was identified per patient. None of patients had lymphatic metastases. No adverse events were identified. Conclusions: An injection of magnetic tracer identified a SLN in 10 % of patients. Therefore magnetic imaging is a feasible, safe, time efficient and reliable method for lymphatic mapping in early stage endometrial cancer.