tbuckley/cabot-search huggingface dataset:
Correlation of hypothyroidism with survival in metastatic renal cancer patients treated with sorafenib or sunitinib.
Authors: L. Riesenbeck, S. Bierer, I. Hoffmeister, T. Koepke, L. Hertle, B. Thielen, E. Herrmann
Journal: Journal of Clinical Oncology (2011)

379 Background: To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su). Methods: Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodtyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH. Results: Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analyses, a poor ECOG status was associated with an unfavorable progression-free survival (PFS) (p&lt;0.0001); similarly high risk MSKCC criteria correlated with a worse PFS (p=0.003). Furthermore, response to therapy was a surrogate parameter (p&lt;0.0001). Twenty-one of 66 (31.8%) patients developed hypothyroidism during treatment, which was associated with a positive prognosis (p=0.032). In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, p=0.018) and hypothyroidism (p=0.01) were independent prognostic parameters. Conclusions: The development of hypothyroidism during treatment might be useful as a clinical predictor of PFS for mRCC patients undergoing treatment with targeted agents. No significant financial relationships to disclose.
Stereotactic body radiotherapy (SBRT) in combination with surgery for primary and metastatic liver tumors.
Authors: Erik Lappinen, Ngoc Thai, Kusum Tom, Akhtar Khan, Ellen Day, William Ross Green, James Christensen, Alexander V. Kirichenko
Journal: Journal of Clinical Oncology (2012)

347 Background: Evaluate the feasibility, safety, and efficacy of SBRT in combination with surgery for primary and metastatic liver tumors. Methods: 12 patients completed hepatectomy and SBRT for either hepatocellular carcinoma (HCC) (3) or metastases from colorectal (4), neuroendocrine (2), uterine (2), or sarcoma (1) primary. All patients with metastases completed chemotherapy. Most patients (7) had resection of their operable metastases, total of 19, and gold fiducials placed in the unresectable lesions, total of 9, to facilitate definitive adjuvant SBRT. One patient with an unresectable metastasis received preoperative SBRT. Two patients with HCC had SBRT as a bridge to liver transplant. Two patients had salvage SBRT for recurrence after surgery. All patients completed 4D-CT for ITV definition and SPECT/CT to define functional normal liver parenchyma volume (NLV). MV-fluoro was performed to confirm tumor/fiducial respiratory motion within the PTV. Results: All patients successfully completed a combination of hepatectomy and SBRT. Seventeen hepatic lesions (≤ 2/patient) were treated with SBRT with a mean PTV 186.0 cc (15.1-803.5). The mean dose was 49.3 Gy (39-60) prescribed to the PTV in 5-6 fractions. With median follow-up of 9.2 months (2.8-15.3) there was no RILD &gt; Grade 1 observed. The most common toxicity was Grade ≤ 2 fatigue. Nine patients had reduced SPECT-NLV vs. calculated NLV by a mean of 487.5 cc (p = 0.0004). In 6 of these, the SPECT-NLV vs. the CT-NLV was reduced by a mean of 253.9 cc (44.6 - 1076.2) reflecting the importance of SPECT functional imaging for SBRT planning. Postoperative morbidity was ≤ Grade 1. All surgical margins were negative. Three patients developed intrahepatic failures post SBRT. However, on follow-up imaging no in-field failures have occurred. Conclusions: The combination of liver SBRT with hepatic resection is safe and effective. It can be used preoperatively to increase resectability or to salvage surgical failures. We also report on the combination of limited hepatectomy for peripheral (including bilobar) hepatic metastases with planned SBRT to unresectable metastatic lesion(s). SBRT planning with SPECT/CT allows identification and preservation of the NLV.
A randomized phase II study of pazopanib in castrate-sensitive prostate cancer: A University of Chicago phase II consortium/DoD Prostate Cancer Clinical Trials Consortium study.
Authors: J. E. Ward, S. Limvorasak, T. Karrison, G. S. Chatta, M. Hussain, D. H. Shevrin, R. Z. Szmulewitz, W. M. Stadler, E. M. Posadas
Journal: Journal of Clinical Oncology (2011)

170 Background: Intermittent androgen suppression (IAS) has been studied as a way of minimizing toxicity from long term androgen deprivation therapy (ADT). Based on previous studies with similar agents, we hypothesized that inhibition of VEGFR would result in prolonged time to PSA progression (TTPP) and allow for longer periods off ADT. Methods: Men with biochemically recurrent, progressive prostate cancer and no evidence of macroscopic metastases were enrolled. They received 6 months of ADT. If at the end of that time the PSA was &lt;0.5 ng/mL (with castrate testosterone levels), they were randomized to pazopanib 800 mg/d or observation. The primary outcome was TTPP, defined as time to a PSA &gt;4.0 ng/mL, at which time they were restarted on ADT. Results: 37 pts met randomization criteria. 18 were randomized to pazopanib. Only 4 pts met the endpoint criteria of TTPP, whereas 13 (72%) pts went off study for other reasons with 1 pt on treatment at study closure. Reasons for discontinuation included drug toxicity (grade 1/2, 9 pts) and patient preference (2 pts). No grade 3/4 toxicity was noted. 1 pt was removed due to pulmonary embolus, 1 pt due to MD discretion and 1 pt due to noncompliance. 19 pts were randomized to observation of which 12 were off treatment when the study was stopped. Only 5 pts met criteria for TTPP, whereas 7 of 12 (58%) dropped out for other reasons, including the frequency of protocol related blood draws and visits (3 pts) and randomization to observation (2 pts), 1 pt was removed per MD discretion and 1 pt transferred care. Due to high dropout rates in both arms, accrual was halted as the primary endpoint could not be measured robustly. Conclusions: Minimizing the long term toxicities of ADT is an unmet need in prostate cancer therapy. Hence clinical interventions in concert with IAS represent an attractive area for drug development. This trial has outlined several barriers that exist in studying this patient population and might help to optimize future studies. Future trial design in this arena should investigate drugs with minimal toxicity and employ a design that maximizes patient convenience while anticipating the low threshold for patient drop out. No significant financial relationships to disclose.
More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia
Authors: Ieva Kantsone, Irina Lucenko, Jurijs Perevoscikovs
Journal: Eurosurveillance (2016)

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey.
Tolerability of neoadjuvant chemotherapy with gemcitabine plus cisplatin in elderly (older than age 65) patients (pts) with muscle-invasive urothelial cancer.
Authors: D. Niedersuess-Beke, B. Gruenberger, T. Puntus, W. Bauer, M. Lamche, P. Schramek, J. G. Meran
Journal: Journal of Clinical Oncology (2011)

296 Background: Urothelial cancer (UC) is a common tumor with a peak in the seventh decade. Locally advanced disease has a significant risk for developing metastases. Neoadjuvant, platinum-containing, combination chemotherapy improves survival over radical cystectomy (RC). Chemotherapy with gemcitabine plus cisplatin (GC) shows equivalent efficacy with less toxicity to methotrexate-vinblastine-doxorubicin- cisplatin (MVAC) in metastatic setting. Methods: We prospectively evaluated 23 elderly pts (8 female, 15 male) with a median age of 72 years, WHO performance status 0/1, with muscle invasive UC who received neoadjuvant GC (gemcitabine 1,000 mg/m 2 days 1, 8, 15 and cisplatin 70 mg/m 2 , day 2 q28) for 3 cycles between 2006 and 2010 prior to RC. Assessments included toxicity of GC, pathologic response, progression free survival (PFS) and overall survival (OS). Results: 21 (91.3%) out of 23 pts finished intended chemotherapy. Two refused chemotherapy due to personal reasons. According to CTCAE guidelines 43.5% developed grade 3 hematologic toxicities; 13% developed grade 4 thrombopenia. Grade 3 non-hematologic toxicities included nausea in 2 patients. In 2 (8.7%) pts grade 4 thromboembolic events occurred. There was no treatment related febrile neutropenia or death. 15 (71.4%) of the pts underwent RC. 5 (23.8%) pts refused RC due to personal reasons. 1 of them agreed second look TURB. 1 patient underwent palliative radiotherapy due to progression of disease. Out of the 16 pts 43.75% achieved pathological response (18.75% pT0 stage and 25% pT1 stage). 56.25% had muscle invasive UC. 18.75% of them nodal positive disease. All 7 pts achieving &lt; pT2 pathologic stage remained progression-free at a median follow up of 16 months. Pts &gt; pT2 stage had a median PFS of 14 months. Median OS was not reached yet. Conclusions: Neoadjuvant GC is a well tolerated regiment in elderly pts and it seems to be less toxic than MVAC. Prophylactic anticoagulation during treatment should be considered. Although pathologic response is lower than in previously published retrospective data we recommend neoadjuvant treatment with GC in elderly pts. [Table: see text]
Clinical Relevance of Low Burden BCR-ABL1 Mutations Detectable By Amplicon Deep Sequencing (DS) in Philadelphia-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Patients (pts): The Type of Mutation Matters
Authors: Simona Soverini, Caterina De Benedittis, Claudia Venturi, Cristina Papayannidis, Manuela Mancini, Katerina Machova Polakova, Domenico Russo, Paola Bresciani, Alessandra Iurlo, Elisabetta Abruzzese, Federica Sorà, Michele Baccarani, Michele Cavo, Torsten Haferlach, Giovanni Martinelli
Journal: Blood (2015)
Thrombotic Events in Adults with Acute Lymphoblastic Leukemia.
Authors: Christine M. Cserti, Joseph Brandwein, Jeffrey H. Lipton, Anne G. McLeod, Hans Messner, Mark D. Minden, Aaron D. Schimmer, Andre C. Schuh, Jack T. Seki, Erik L. Yeo, Qi-Long Yi, Richard A. Wells
Journal: Blood (2004)
Effect of octreotide LAR on quality of life of 93 Hungarian patients with neuroendocrine tumors.
Authors: Tibor Gyökeres, Sonia Pulgar, Neha Singh, Vanessa Q. Passos, Peter Kelemen
Journal: Journal of Clinical Oncology (2012)

362 Background: Studies have shown that health-related quality of life (HRQoL) of patients with neuroendocrine tumors (NET) is lower compared to the general population in the US and Norway. Secretory symptoms associated with functional NET (diarrhea/flushing) contribute to worsened HRQoL but may be controlled with the somatostatin analog octreotide long-acting repeatable (LAR). To date, there have been limited assessments of specific drug effects on HRQoL in patients with NET. The purpose of this study was to assess the effect of octreotide LAR treatment on HRQoL. Methods: 93 Hungarian patients with gastroenteropancreatic NET who were treated with octreotide LAR participated in a multicenter observational study from 2005 to 2007. At study entry and 4 quarterly follow-up visits, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire. A mixed model was used to analyze the data and confirm significance. Results: 91 patients (mean age = 61 years) were evaluable for QoL assessments. Overall, patients reported improvements in diarrhea, global health status, emotional functioning, and financial difficulties but worsening in role functioning, pain, and insomnia. There were some differences in trends, depending on the tumor site, but diarrhea still improved in all patient categories. Women reported lower global health status compared to men, including more fatigue, nausea/vomiting, pain, dyspnea, and constipation. Elderly patients &gt;70 years did not report any lessening of overall global health status scores compared to younger patients; older patients did experience less nausea/vomiting and pain but more constipation and diarrhea. In addition, patients diagnosed &lt;2 years had slightly lower global health status than patients diagnosed &gt;2 years earlier. Conclusions: Patients with NET who were treated with octreotide LAR had improvements in global health status and diarrhea. Interesting trends were noted in different patient populations, depending on tumor site, gender, or age. Additional analysis is planned to assess changes as measured by the GI NET disease-specific module of EORTC that was also applied to patients.
Evaluation of whole-body FDG-PET in breast cancer screening.
Authors: S. Nishizawa, H. Kodama, H. Okada
Journal: Journal of Clinical Oncology (2011)

66 Background: The utility of whole-body FDG-PET for the detection of breast cancers in a screening program is not well investigated. Methods: We analyzed data from a cancer screening program including whole-body FDG-PET performed for consecutive 2065 asymptomatic women (age: 40 to 80 y.o. with mean ± SD of 56.1 ± 8.6 y.o.) without a previous history of breast cancer. They underwent the initial screening between September 2003 and December 2008. The screening included neither mammography nor ultrasonography of the breast. Final results of cancers and/or follow-up data more than 1 year following the screening were available in 1822 of the 2065 (88.2%: 941 by the following screening and 881 by the response to questionnaires). Data of the second screening in 670 women (age: 55.0 ± 8.0 y.o.) of the 941, who didn’t have cancer at the initial screening and received the second screening by December 2008 and within 2 years of the initial screening were also analyzed. Final results and/or follow-up data more than 1 year were available in 642 of the 670 (95.8%: 573 by a subsequent screening and 69 by the response to questionnaires). Results: Data were analyzed as of the end of 2010. In 2 years after the initial screening, 57 cancers of a variety of organs including 12 of the breast were confirmed. Nine (stage 0: 1, I: 7 and IIA: 1) of the 12 were proven in 29 women with PET positive results and 3 (stage I: 1, IIA: 1 and not available: 1) in 2036 women with PET negative results. In 2 years after the second screening, 9 cancers including 4 of the breast were confirmed. Three of the 4 (stage 0: 1, I: 1 and IIB: 1) were diagnosed in 9 women with PET positive results and 1 (stage I) in 661 with PET negative results. Two of the 4 PET negative cancers were diagnosed after developing symptoms and the remaining 2 were detected by another screening. Sensitivity, specificity, positive and negative predictive values and false positive rate of the initial screening were 75.0% (9/12), 99.0% (2033/2053), 31.0% (9/29), 99.9% (2033/2036) and 1.0% (20/2053), respectively. Conclusions: Whole-body FDG-PET had the capability to screen the breast with a very low false positive rate and high positive and negative predictive values, and could detect breast cancers of asymptomatic women at early stages with reasonable sensitivity.
Influence of breast cancer CME on provider knowledge and competence.
Authors: T. B. Stacy, A. A. Heintz, K. Dopson, K. McLane, M. E. Haas
Journal: Journal of Clinical Oncology (2011)

214 Background: Due to the volume and pace of scientific advances within oncology, the timely dissemination of clinical trial results and discussion regarding the appropriate incorporation into therapeutic decision making is necessary to provide the highest quality patient care. Increasing awareness in the breast cancer community on similarities and differences amongst practice management strategies helps to identify practice patterns and benchmark individual knowledge and competence against one’s professional peers. Methods: During 2010 and 2011, educational outcomes assessments were gathered during 83 independent continuing medical education (CME) activities held within community and academic institutions across the USA. Participants were asked a series of case-based questions via an audience response system to assess baseline knowledge, competence, and identify practice patterns. Assessments were repeated post a 1-hour CME certified activity, with an additional 6-week electronic follow-up. Barriers to implementing the information learned were also captured. Educational gaps were identified through documentation and comparison of current best practices versus actual participant responses. Results: To date, a total of 1,515 healthcare providers have participated in the initiative. Number of years in practice ranged from &lt;10 to &gt;30. The number of breast cancer patients seen per month ranged from ≤10 to &gt;40. Provider competency in applying recent literature to the patient care setting was both assessed and measured. Results of neoadjuvant data knowledge, adjuvant therapy selection, relapsed HER2+ disease treatment strategies, and competence in discussing efficacy and safety data from recent clinical trials will be presented. Participants reported a number of barriers to applying data learned at the activities into clinical practice. Responses included lack of reimbursement, treatment side effects, newness of treatment data, and perceived efficacy. Conclusions: The results suggest the education of providers on the most currently available clinical trial results and expert discussion of how to optimize translation of this information into patient care increases breast cancer provider knowledge and competence.
Hypercholesterolemia and Its Association with Enhanced Stem Cell Mobilization and Harvest After High-Dose Cyclophosphamide + G-CSF
Authors: Martina Crysandt, Ralf-Dieter Hilgers, Sabine von Hobe, Albrecht Eisert, Edgar Jost, Jens Panse, Tim H. Brummendorf, Stefan Wilop
Journal: Blood (2010)
Clinico-Immunobiologic Study By a Prospective Open-Label Clinical Trial of Deferasirox before &amp; after Allogeneic HSCT in Adult Patients with AML - Preliminary Analysis Focusing on Outcomes with Immunocyte Subsets (I) -
Authors: Heeje Kim, Jae-Ho Yoon, Seung-Ah Yahng, Sung-Eun Lee, Seung-Hwan Shin, Byung-Sik Cho, Jong-Wook Lee, Woo-Sung Min
Journal: Blood (2014)
Sixty seconds on . . . scurvy
Authors: Susan Mayor
Journal: BMJ (2016)

You might think so. Scurvy was blamed for the deaths of at least two million sailors between the 16th and 18th centuries. James Lind, a Royal Navy surgeon, is credited with carrying out the first ever controlled trial, with a study published in 1753 showing that scurvy could be treated with citrus fruit.1

Not quite. Physicians were unconvinced by the evidence and took no action until …
Preoperative Evaluation for Noncardiac Surgery
Authors: Steven L. Cohn
Journal: Annals of Internal Medicine (2016)

This issue provides a clinical overview of preoperative evaluation for noncardiac surgery, focusing on risk factors, elements of evaluation, medication management, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Plasma cytokine and angiogenic factors (CAFs) predictive of clinical benefit and prognosis in patients (Pts) with advanced or metastatic renal cell cancer (mRCC) treated in phase III trials of pazopanib (PAZO).
Authors: Y. Liu, H. T. Tran, Y. Lin, A. Martin, A. J. Zurita, C. N. Sternberg, R. G. Amado, L. N. Pandite, J. Heymach
Journal: Journal of Clinical Oncology (2011)

334 Background: PAZO is a multikinase inhibitor approved for the treatment of mRCC. From phase II study of PAZO in mRCC (VEG102616), plasma CAF analysis from 3 different platforms (cross platform correlation r &gt;0.70) revealed several candidate CAFs including HGF, IL-6, IL-8, TIMP-1, VEGF, E-Selectin and OPN were found to be significantly correlated with clinical benefit (Tran ASCO 2010, #4522). To validate these findings, plasma were analyzed for CAFs from mRCC pts enrolled in phase III randomized, placebo controlled trial with PAZO where progression-free survival (PFS) of 9.2 months of PAZO and 4.2 months of placebo (hazard ratio:0.46 p&lt;.0001) and overall response rate 30% was observed (Sternberg, JCO, 2010). Methods: Plasma samples (n=344) from phase III randomized, placebo-controlled trial (VEG105192) were analyzed for candidate CAFs by a CLIA-certified laboratory (Aushon Biosystems, MA). These markers of PAZO and placebo arms were correlated with PFS by Cox regression and plotted in Kaplan Meier by using median concentration of each marker as a cutoff. Results: Higher levels of IL-8 (p&lt;0.006), HGF (p&lt;0.01), OPN (p&lt;0.001) and TIMP-1 (p&lt;0.006) were associated with shorter PFS in PAZO treated pts. Higher levels of all these markers except HGF were also associated with shorter PFS in the placebo arm (IL-8 (p&lt;0.002), OPN (p&lt;0.001), IL-6 (&lt;0.001), TIMP-1 borderline at p= 0.052) and were therefore prognostic. Only IL-6 was predictive of PFS benefit; pts with high IL-6 had a greater relative benefit from PAZO compared to placebo with a HR of 0.32 in the high IL-6 group and 0.57 in the low IL-6 group (p value for interaction 0.009). Conclusions: This study validated HGF, IL-8, OPN, and TIMP-1 as markers associated with clinical benefit with PAZO treatment. IL-8 and OPN were confirmed as prognostic markers in the placebo arm and IL-6 was both a prognostic marker and predictive marker for pazopanib therapy. [Table: see text]