tbuckley/cabot-search huggingface dataset:
Efficacy of cetuximab-containing chemotherapy with or without bevacizumab in prior chemotherapies.
Authors: Yasuyoshi Sato, Satoshi Matsusaka, Izuma Nakayama, Takeru Wakatsuki, Mariko Ogura, Masato Ozaka, Mitsukuni Suenaga, Eiji Shinozaki, Keisho Chin, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2014)

e14591 Background: Cetuximab and bevacizumab have been shown to improve survival of metastatic colorectal cancer (mCRC) patients, but the best sequence of them is still unknown. The aim of this study was to evaluate survival of mCRC patients treated with cetuximab after bevacizumab failure compared to non-treatment of bevacizumab. Methods: A total of 323 mCRC patients treated with cetuximab between March 2006 and July 2013 in our hospital, of which 190 (107 male, 83 female; median age 60.7 years) were enrolled in a retrospective study. Forty-seven were treated with cetuximab-based therapy as second-line; 21 had prior bevacizumab and 143 were treated as third and more line; 109 had prior bevacizumab. Kaplan-Meier method with log-rank test and cox regression analysis were performed to evaluate overall survival (OS) and progression-free survival (PFS) of each. Results: Median follow-up time was 11.2 months in second-line cetuximab-based chemotherapy and 13.0 months in third and more line. In univariate analysis, median PFS were significantly longer in patients without prior bevacizumab compared to those with prior bevacizumab (4.4 vs. 3.1 months; HR (95% CI) 1.9 (1.0-3.6), p=0.048 and 8.4 vs. 4.8 months; HR (95% CI) 1.9 (1.2-3.0), p=0.004). In multivariate analysis adjusted for baseline characteristics, bevacizumab+/- before cetuximab-based chemotherapy were significant in PFS [HR (95% CI) 1.7 (1.0-2.7), p=0.03] in third and more line. Overall, prior bevacizumab use were not associated with OS in both line. Conclusions: Cetuximab could be more effective without prior bevacizumab; prior bevacizumab use may decrease the efficacy of cetuximab.
Lower urinary tract symptoms (LUTS) in prostate cancer (PC) patients treated with GnRH antagonist compared to agonist: Results of a pooled analysis.
Authors: Malcolm David Mason, Zsolt Bosnyak, Anders Malmberg, Anders Neijber
Journal: Journal of Clinical Oncology (2014)

e16017^ Background: PC is commonly associated with LUTS. GnRH agonists or antagonists are widely used as primary treatment in advanced PC and/or to reduce prostate volume (TPV). The objective of this analysis was to compare efficacy of the GnRH antagonist degarelix with the GnRH agonist goserelin in improving LUTS in patients with different stages of PC. Methods: Pooled data were analyzed from three phase 3, randomized clinical trials with patients receiving once-monthly treatment for 12 weeks with either degarelix (n=289; 240/80 mg) or goserelin (n=174; 3.6 mg) + bicalutamide (50 mg) for initial flare protection. LUTS symptoms were evaluated based on IPSS at weeks 4, 8, 12 and compared to baseline. Clinically relevant LUTS relief was defined by at least 3-point decrease in IPSS. Adjustments were made for potential confounders. Prostate cancer stages were categorized by TNM as localized: T1/2 and NX/0 and M0; advanced: T3/4 and (NX/0 and M0) or (N1 and M0) or M1. Adverse events were assessed throughout the trials. Results: Significantly greater declines in IPSS were seen for patients on degarelix, compared to goserelin at week 12 (adjusted difference: -1.24; 95% CI: -2.33;-0.14; p=0.03) corresponding with a greater proportion of patients on degarelix with clinically relevant LUTS relief (OR: 1.52; 95% CI: 0.92-2.51). The clinical benefit for the antagonist therapy was especially pronounced in patients with moderate-to-severe LUTS (IPSS >=13 at baseline) (OR: 2.31; 1.19-4.47 p=0.01) and advanced prostate cancer (OR: 2.36; 1.10-5.04 p=0.03). A two-fold likelihood (OR: 2.03; 1.14-3.60 p=0.02) for an early (week 4) clinically relevant LUTS relief was seen with degarelix compared to goserelin. No difference in castration efficacy (testosterone and PSA), TPV or urinary tract infection-related adverse events (2%) was seen between the treatment groups. Conclusions: Besides similar androgen deprivation degarelix was associated with an early, significant and clinically more pronounced improvement of LUTS, especially in patients with moderate-to-severe LUTS or advanced prostate cancer. This symptomatic benefit may be linked to the different mechanism of action. Clinical trial information: NCT00833248.
Clinical Characteristics of GNB1 and GNAS Mutations in an Unselected Cohort of 6,343 Patients with Hematologic Abnormalities
Authors: Rahul S. Vedula, Marlise R. Luskin, Kevin Copson, Priti Kumari, Anne Charles, Annette S. Kim, Elizabeth A Morgan, Gregory A. Abel, Richard M. Stone, Andrew A. Lane, R. Coleman Lindsley
Journal: Blood (2018)
Phase I/II Trial of Bendamustine, Ixazomib and Dexamethasone (BID) in Patients (pts.) with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Binod Dhakal, Anita D'Souza, Mehdi Hamadani, Carlos E. Arce-Lara, Katrina Schroeder, Saurabh Chhabra, Nirav N Shah, Katelyn Gauger, Taylor Keaton, Marcelo C. Pasquini, Parameswaran Hari
Journal: Blood (2018)
Association of natural killer (NK) cell exhaustion with melanoma progression.
Authors: Ines Esteves Domingues Pires Da Silva, Anne Gallois, Kevin P. Lui, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Judy Zhong, Nina Bhardwaj, Iman Osman
Journal: Journal of Clinical Oncology (2014)

9099 Background: Recent success of immunotherapies targeting the exhaustion markers CTLA-4 and PD-1 has inforced the role of CD8+T cell exhaustion in advanced melanoma patients. T cell exhaustion, has been extensively studied, however little is known about NK cell exhaustion in the same context. In this project, we defined NK cells phenotype in different stages of melanoma to examine its role in melanoma progression. Methods: NK cells were purified from the peripheral blood of a prospectively-enrolled cohort of 100 melanoma patients: stage I (n=56), stage II (n=21) and stages III/IV (n=23); in addition to 25 healthy donors. NK cells were characterized for the expression of activating (NKG2D and NKp46) and inhibitory receptors (Tim-3, KIRB1 and KIRNKAT2), function (cytotoxicity, IFN-γ production and proliferation) and the intracellular expression of the transcription factors (T-bet and Eomes). We then tested the association between NK cell phenotype and clinicopathological variables associated with melanoma prognosis. Unpaired T test was used to compare two groups, and ANOVA to compare more than two groups. Results: NK cells gradually develop a phenotypic and functional profile consistent with progressive exhaustion, from stage I to stage IV characterized by: 1) up-regulation of inhibitory receptors (Tim-3, KIRB1 and KIRNKAT2); 2) down-regulation of activating receptors (NKG2D and NKp46) and transcription factors (T-bet and Eomes); 3) loss of IFN-γ production,proliferation and cytotoxicity. Interestingly, the expression of Tim-3 and KIRB1 is higher, while the cytotoxic ability is reduced in patients with melanomas thicker than 1mm (Tim-3 – p=0.007; KIRB1 – p=0.03; cytotoxicity – p=0.05). Higher Tim-3 expression is associated with ulceration (p=0.009) and with mitosis (p=0.001). Moreover, higher expression of Tim-3 and KIRB1, and a lower cytotoxic ability is associated with local or distant metastases (Tim-3 – P=0.002; KIRB1 – p=0.0009; cytotoxicity – p=0.0005). Conclusions: Data demonstrate that NK cells become progressively exhausted in the context of melanoma progression. NK cells start acquiring this phenotype in early stages which suggests that targeting them earlier can be be a novel therapeutic strategy.
Abstract 21336: Comparison of the Serial Levels of the Sofa and Apache II Score for Predicting Neurologic Outcome of out of Hospital Cardiac Arrest Survivors With Targeted Temperature Management
Authors: SANG-IL KIM, Won Young Kim, Youn-Jung kim, Seung Mok Ryoo
Journal: Circulation (2017)

Introduction: Sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APAHCE) II score are known as useful prediction tools for mortality in critically ill patients. This study aimed to compare the prognostic value of serial levels of SOFA and APAHCE II score for the neurologic outcome in comatose out-of-hospital cardiac arrest (OHCA) survivor treated with targeted temperature management (TTM). Methods: This single-center, registry-based, retrospective cohort study which included consecutive adult (≥18 years) comatose OHCA survivors with TTM was conducted in January 2010 and December 2015 at a tertiary care university-affiliated hospital emergency department. SOFA and APACHE II score were calculated at initial (D0), day 1(D1), day 2(D2), day 3(D3), day 5(D5), day 7(D7) after intensive care unit (ICU) admission. The primary outcome was 28-day good neurologic outcome and secondary outcome was 28-day survival. Prognostic value of SOFA and APACHE II score was analyzed using receiver operating characteristic curve. Results: A total of 143 patients, 62 patients (43.4%) had a survival and 34 patients (23.8%) had good neurologic outcome at day 28. SOFA and extracerebral SOFA scores did not show difference between good neurologic outcome two groups. Both SOFA and APACHE II score had significantly higher in non-survival group than survival group. However, for neurologic outcome, APACHE II score had a significant difference between good and poor neurologic outcome groups at D0, D1, D2, D3, D5, D7, but SOFA did not. APACHE II score at D3 had a highest prognostic values for predicting poor neurologic outcome (area under the cure of 0.793 [95% CI; 0.702-0.884]), its optimal cut-off point was 15. Conclusions: In the present study, illness severity during early post cardiac arrest period, as assessed by APACHE II score was associated with poor neurologic outcome; especially APACHE II score after ICU day 3 may help clinicians assess the neurologic outcome of post cardiac arrest patient.
Effectiveness of nurse-led and physician-assisted homecare provided from a rural cancer center in India evaluated using the palliative care outcome scale.
Authors: M.S. Biji, Santam Chakraborty, NR Sindhu, Shibimol Thomas, Subhradev Sen, Milind Kumar, Satheesan Balasubramaniam
Journal: Journal of Clinical Oncology (2014)

e20544 Background: Palliative care services are usually provided by trained nurses and volunteers in India. Home care services in our center are provided through trained nurses with palliative care physician providing assistance when required for new complaints or interventions. Methods: A prospective study was conducted in all patients under our home care between 02/01/2012 to 08/31/2013. Trained palliative care nurses conducted 4 visits at 2 week intervals and sought physician assistance when required. Primary endpoint was change in symptoms and well being measured using patient reported Palliative care Outcome Scale score (POS), with a reduction in the POS score indicating an improvement. Differences in total POS score were tested using the Friedman test. Linear regression was used to find factors significantly influencing relative change in POS scores between first and last visit. P values < 0.05 were taken as significant. Results: 111 patients were recruited in the study period mainly having head neck (32%), gastrointestinal (23%) and lung cancers (14%). 27 patients (24.3%) died between the 1st and 4th follow-up visits. The Table shows the changes in POS score at each visit. Improvement was noted in all subdomains of the POS score across the visits. None of the patients had an increase of the POS score. Prevalence of bedsore reduced from 20.5% in 1st visit to 9.5% in fourth visit. Proportion of patients with ryles tube (16.8% vs 14.6%), catheter (57.9% vs 56.6%) and ascites (6.5% and 7.1%) remained stable between first and fourth visits. Mean reduction in POS was 78.3% (SD 20.4%). Patients without comorbidities, with ascites and infected wound in first visit had a significantly poorer reduction in POS scores (P=0.008, 0.048 and 0.0001 respectively). Conclusions: Effectiveness of this unique model of homecare is reflected by significant reduction in total POS scores. However patients with infected wounds and ascites had less reduction in POS scores, indicating need for further improvement in service delivery. Mean (standard deviation) of POS scores at each visit. Visit 1 Visit 2 Visit 3 Visit 4 P Value POS 9.62 (4.45) 4.07 (2.94) 1.85 (1.85) 1.32 (1.42) < 0.001
Audio visual recording of informed consent: Novel mandatory regulatory compliance for clinical trials in India.
Authors: Purvish M. Parikh, Kumar Prabhash, Kanaka Govind Babu, Gouri Shankar Bhattacharyya, Khurshid Mistry
Journal: Journal of Clinical Oncology (2014)

e17672 Background: The Drugs Controller General (India) [DCG(I)] (Equivalent to US FDA) has made it mandatory to perform Audio Visual (AV) recording of the informed consent for all clinical trials in India. Methods: We compared our standard operating procedure to the draft guidelines developed by CDSCO to check for compliance with regulatory requirements, ethical standards and archival. The differences of relevance were documented. The time required to comply with these SOPs was also estimated and compared. Results: The SOP developed by us is a 13 page document with 7 sections that contains details of the procedure, applicablility, as well as specifics of what equipment, personnel and environment is required for the recording.Variations for five circumstances were outlined based on whether the potential participant was literate or not, whether the consent was being administered in a language common to the parties concerned or not and whether a legally acceptable representative was necessary or not. The SOP also contains details to ensure confidentiality and privacy. The checklist prepared consisted of 24 tems to ensure that the AV recording documented that the written consent process was informed, voluntary and impartial. The two documents were found to have several features with significant differences. This related to the topics of preamble and compliance, objective, information for prospective study subjects, scope, principles of privacy, consent for AV recording, procedure of recording, quality of recording, storage and archival as well as the checklist. Estimates of the time required to comply varied from 8 minutes to 86 minutes. Conclusions: The SOP was developed keeping in mind all relevant orders, regulations, laws and guidelines and have been made available online. Since we are faced with unique legal and regulatory requirements that are unprecedented globally, this SOP will allow the AV recording of the informed consent to be performed, archived and retrieved to demonstrate ethical, legal and regulatory compliance.
Low Hemoglobin Increases Risk for Stroke, Kidney Disease, Elevated Estimated Pulmonary Artery Systolic Pressure, and Premature Death in Sickle Cell Disease: A Systematic Literature Review and Meta-Analysis
Authors: Kenneth I. Ataga, Victor R. Gordeuk, I. Elaine Allen, Jennifer Colby, Kimberly Gittings, Irene Agodoa
Journal: Blood (2018)
Evaluation of changes on tumor-infiltrating lymphocytes and regulatory T-cells in tissue and peripheral blood after neoadjuvant chemotherapy in breast cancer patients and relation with pathologic complete response.
Authors: Luis de la Cruz Merino, Antonio Barco Sanchez, Jose Ibanez Martinez, Javier Brugal Molina, Fernando Henao, Esteban Nogales, MªÁngeles Lobo Acosta, V. Sanchez Margalet, A. Nieto Garcia
Journal: Journal of Clinical Oncology (2014)

3042 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. We designed a protocol to analyze immune profile before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response (pCR). Methods: From March 2011 to January 2014, 47 patients (18 Her2+/ 29 Her2-) with T2-4 N0-3 breast carcinoma treated with neoadjuvant chemotherapy in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study. CD3+, CD8+, CD8-16-56+ and Foxp3+ cell infiltrates were detected by immunohistochemistry before and after neoadjuvant CT in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle of CT to determine the immunophenotype profile. Cell populations were determined by flow cytometry analysis of whole blood, including the study of CD3-CD4-CD25low and CD3-CD4-CD25high (regulatory) T cells. Results: By January 2014, 47 patients (18 Her2+/29 Her2-) were operated. Pathological complete responses (pCR) or near pCR (grade 4/5 Myller&Payne) were attained in 20 patients (42,6%). pCR was achieved in 66,66% (12/18) of tumors overexpressing Her2, but in only a 27,5% (8/29) of Her2-negative tumors. Absence and/or disappearance of Tregs in tissue (Black grading system=0) was more frequent after neoadjuvant CT (11,11 vs 62,2%). Average whole blood CD3-CD4-CD25high (regulatory) T cells were 126,36 before CT and 91,19 cells/microliter after neoadjuvant CT (p 0,010). Overall Tregs diminished in the pCR and non pCR groups without statistically significant differences. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates in tissue and CD3-CD4-CD25high (regulatory) T cells in peripheral blood in all the population. Although differences among subgroups (pCR/non-pCR and Her2+/Her2-) were not statistically significant, these data support the role of Tregs as an interesting biomarker with eventual therapeutic implications.
Retrospective analysis of toxicities associated with low-dose cisplatin and docetaxel and SWOG protocol in concurrent chemoradiotherapy for locally advanced non-small lung carcinoma.
Authors: Pinky Baghi, Ina Nordman, Yolande Cox, Fiona Louise Abell, Jane Ludbrook
Journal: Journal of Clinical Oncology (2014)

e18524 Background: Concurrent chemoradiotherapy is the standard of care for majority of medically fit locally advanced nonsmall cell carcinoma (IIIA, IIIB). The optimal chemotherapy regimen for use with concurrent thoracic radiotherapy is not known due to a paucity of phase III data in this context. Phase II studies have demonstrated high disease response rate when weekly cisplatin and docetaxel is administered concurrently with radiotherapy. SWOG chemoradiotherapy regimen with cisplatin and etoposide, which is commonly used has not been compared to cisplatin doublet in phase III trial. In our centre we have adopted local chemoradiation protocol with low dose cisplatin (20 mg/m2) and Docetaxel( 20 mg/m2)[CD] in addition to using SWOG protocol. We did retrospective analysis of toxicities associated with these regimens. Methods: Oncology pharmacy dispensing records searched to identify patients treated with either SWOG or CD protocol. Data correlated with radiation oncology records. Toxicity graded according to NCI guidelines. Staging recorded as documented. Results: Sixty eligible patients received CD and 18 had SWOG. In CD group, 58 % patients were staged IIIA,40 % stage IIIB vs 43%, 7 % respectively in SWOG. With CD grade3/4 hematological toxicities less than 2%. Grade3/4 esophagitis seen in 36 % cases. 20% patients had chemotherapy delays. 73% patients completed 6 weeks of planned treatment. One treatment related death occurred. In SWOG protocol, Grade 3 and 4 neutropenia seen in 28 % and 16% patients. Grade 3 thrombocytopenia in 16% cases. 33% had grade ¾ esophagitis. 50% patients required chemotherapy modifications. 28% patients had moderate to severe renal function during treatment. Conclusions: Limitations as retrospective data. Patients staged according to TNM staging 6 and 7. Fewer patients received SWOG. Some patients on SWOG received pegfilgrastim support. In CD 42% patients received either induction or consolidation chemotherapy. Low dose CD associated with lower haematological toxicities. Oesophagitis significant toxicity with both. Prospective study required to find optimal regimen.
“Lost to follow-up” among adult cancer survivors.
Authors: Rahul Gosain, Amitoj Singh Gill, Ashtami Banavali, Shruti Bhandari, Joseph Abraham, Kenneth David Miller
Journal: Journal of Clinical Oncology (2014)

e20595 Background: Long-term survivorship care is especially important for patients who have received chemotherapy but there is little data on how many patients are lost to follow-up (LFU). The purpose of this study was to determine what proportion of cancer survivors are LFU at 5 years after treatment, the timing of LFU after diagnosis, and the characteristics of those who do not continue survivorship care. Methods: Adult patients with cancer who were treated with chemotherapy at a large community teaching hospital in 2006 and 2007 were identified and linked with State tumor registry data. Hospital medical records were reviewed to obtain information on demographics, diagnosis, treatment, and date of last follow up visit. Characteristics of patients with 5 or more years of follow-up care were compared to those who were LFU. Results: 487 patients received chemotherapy and 304 died (62.4%) during the 5-year follow-up period. Of the 183 cancer patients who were known to be alive at five years, 92 (50.3%) were LFU and 50% (46/92) of this LFU group were LFU within 1 year of diagnosis. At 5 years, follow-up care was continuing for 55% of women, compared to 39% of men (p<0.05). The highest proportion of follow-up was observed among lung cancer patients (84.2%), followed by patients with breast cancers (63.2%) and GI cancers (40%). Patients with hematological cancers had the lowest follow-up proportion at 5 years (28.8%) (p<.05). Follow-up was not significantly associated with age (p=0.48), insurance status(p=0.29) and race(p=0.06). Conclusions: It is estimated that 65% of the cancer survivors in the United States are 5 or more years beyond their diagnosis but there are little data on oncology follow-up rates. In our retrospective study of 183 patients who were treated with chemotherapy only 49.7% continue to follow up at their treatment center. LFU has important implications in planning long-term care strategies for cancer survivors and in survivorship research.
Abstract 18821: Extreme Elevations in Both HDL-C and Lp(a), Adiposity, and Subclinical Atherosclerosis in a Multi-ethnic Population-based Cohort: Observation From The Dallas Heart Study
Authors: Nimish N Shah, Ian J Neeland, Parag H Joshi, Amit Khera, Colby Ayers, Anand Rohatgi
Journal: Circulation (2017)

Introduction: Higher HDL-C is considered atheroprotective; however, extremely elevated HDL-C may confer increased atherosclerotic cardiovascular disease (ASCVD) risk. Elevated lipoprotein (a) [Lp(a)] is a known independent risk factor for ASCVD. We hypothesized that those with both extremely elevated HDL-C and Lp(a) would have accentuated adverse metabolic and atherosclerosis phenotypes. Methods: Participants were included from the probability-based multi-ethnic Dallas Heart Study who had risk factor measurements, MRI, DXA, and coronary calcium (CAC). High HDL-C was defined as greater than the 90th race- and sex-specific percentile, and high Lp(a) was defined as greater than the 80th race- and sex-specific percentile. Four groups were constructed to compare risk factors: high HDL-C/high Lp(a), high HDL-C alone, high Lp(a) alone, and neither high. Multivariable adjusted linear regression models were used to assess the cross-sectional association between high HDL-C/high Lp(a) relative to the neither high gr...