Dreaming of a Cure

BackgroundParenteral nutrition (PN) is used as nutritional support in patients that are malnourished, critically ill, and/or have a nonfunctional gut. Patients receiving PN are at increased risk for both infectious and noninfectious catheter complications often leading to increased morbidity and mortality. Risk factors for catheter complications in patients receiving PN are often variable and poorly understood.MethodsWe conducted retrospective study among cancer patients who received PN between January 1, 2013 and December 31, 2015 at the University of Texas MD Anderson Cancer Center. Rate and prevalence of central line associated blood stream infection (CLABSI) and noninfectious catheter complications were assessed. Additionally, prevalence and time-to-infection of causative pathogens were evaluated. Multivariate logistic regression analyses were conducted in a sample of the PN population to identify risk factors for both infectious and noninfectious catheter complications.ResultsWe identified 46 CLABSI cases in 38 patients of the 1,762 patients receiving PN (1.73 episodes of CLABSI per 1000 PN days). Gram-positives (37.84%) and yeast (29.73%) were the most common pathogens, with catheter-related Candidemias occurring earlier than gram-positive or gram-negative CLABSI. Noninfectious catheter complications occurred in 56 patients (38.6%). Multivariate analysis identified age, GVHD, and history of occlusion in the same catheter, as well as intestinal failure and long-term PN use as significant risk factors for CLABSI and noninfectious catheter complications, respectively.ConclusionPatients receiving PN are at higher risk for both infectious and noninfectious catheter complications. Compared with national averages of CLABSI, the prevalence of catheter-related Candidemias in the PN cancer patient population was increased. This study highlights the need for development of more effective targeted preventative interventions.DisclosuresJ. Rosenblatt, Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a and Shareholder, Licensing agreement or royalty; UT MD Anderson Cancer Center: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a s and Scientific Advisor, Licensing agreement or royalty; I. Raad, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant; Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Raad is a s and Shareholder, Licensing agreement or royalty.

Recommendations for Post-Prostatectomy Radiation Therapy in the United States Before and After the Presentation of Randomized Trials

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

Reply by Authors.

BackgroundThe gut microbiome has been associated with response to anti-PD-1 therapy in melanoma, lung cancer, and kidney cancer. Small clinical trials combining gut microbiome modulation via fecal microbiota transplantation (FMT)...

Author details 1Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA. 2Department of Cell and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA. 3Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 13 Taishogun Nishitakatsukasa-Cho, Kita-ku, Kyoto 403-8334, Japan. 4PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. 5Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8673, Japan. 6Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 78030, USA. 7Center for RNA Interference and Noncoding RNA, University of Texas MD Anderson Cancer Center, Houston, TX 78030, USA. 8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 78030, USA. 9Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX 78229, USA. Published: 21 December 2012

CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.

Waun Ki Hong and John Mendelsohn were vastly different characters, with different backgrounds and strengths. Yet once together at The University of Texas MD Anderson Cancer Center in Houston, the combination of these 2 great men had an enormous impact on reinvigorating the institution and generations of physicians, scientists, and patients.

Anaplastic thyroid carcinoma (ATC) is an aggressive disease that requires rapid diagnosis and multimodality treatment. Recent advances in targeted therapeutics have provided ATC patients with previously unavailable treatment options, which may improve clinical outcomes in the coming years. Continued development of high-throughput next-generation sequencing provides clinicians with an unparalleled ability to characterize the genomic background of tumors in order to guide treatment selection and clinical trial enrollment. Twenty-three patients with ATC treated at the University of Texas MD Anderson Cancer Center between August 2015 and April 2016 were evaluated. All patients underwent next-generation sequencing using an institutional tissue-based DNA platform (50 genes) and a commercially available cell-free circulating DNA (cfDNA) platform (70 genes). Sequencing data were successfully obtained for both platforms on all patients. The most commonly mutated genes noted on both platforms were TP53 (15/23; 65%) and BRAF (11/23; 48%). Concordance between the tumor and cfDNA data was high for BRAF, PIK3CA, NRAS, and PTEN and moderate for TP53. Concordance was highest in patients who underwent dual-platform sequencing prior to initiation of definitive treatment, and lowest in patients who underwent cfDNA analysis following treatment. Nineteen patients had treatment at the University of Texas MD Anderson Cancer Center following cfDNA sequencing. One patient was observed, and three patients opted for hospice. At the time of last contact, 15/23 (65%) patients were alive. Next-generation sequencing platforms offer clinicians an opportunity to identify targetable oncogenic events in ATC. To the authors' knowledge, this is the largest sequential cohort of ATC patients who have undergone targeted genomic profiling. Based on these data, utilization of both tumor-based and cfDNA analysis in the context of clinical-trial development and application is recommended. Integration of these or similar platforms in clinical-trial implementation may have the potential to transform clinical outcomes for patients with ATC.

Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX Disclosure: There is no conflict of interest or other disclosures. Reprints: Horiana B. Grosu, MD, MPH, Department of Pulmonary Medicine, Unit 1462, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: [email protected]).

At the present time, we do not have access to predictors of response to hypomethylating agents. MicroRNA (miRNAs) are noncoding RNAs of 19–25 nucleotides in length that regulate gene expression by inducing translational inhibition and cleavage of their target mRNAs through base pairing to partially or fully complementary sites. Altered miRNA expression has been documented in multiples types of leukemia [1]. Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous disorder characterized by differentiation arrest and malignant proliferation of clonal myeloid precursors. Specific miRNA signatures are associated with cytogenetics and prognosis in AML [2]. Recently it has been reported that pretreatment expression levels of miR-29b are associated with clinical response in patients with AML treated with a 10-day schedule of decitabine [3]. miR-29b is involved in the regulation of DNA methylation and is down regulated in AML [3, 4]. The hypothesis is that patients with higher miR-29b levels would have lower levels of DNA methyltransferase, less hypomethylation, and potentially increased sensitivity to decitabine [3]. This hypothesis is in line with previous observations associating lower levels of p15 methylation with response to decitabine based therapy [5].The findings of Blum et al. [3] are therefore very significant as detection of miR-29b, if validated, could be used to select hypomethylating-based therapy in AML. To follow on these observations, we have analyzed miR-29b and miR-101 expression levels in a cohort of patients with AML or high-risk myelodysplastic syndrome treated in a phase I/II study of the combination of 5-azacitidine (5-AZA), valproic acid, and ATRA [6]. We analyzed 45 patients, 28 of which had not received prior therapy. The characteristics of these patients have been previously reported [6]. Eight (29%) patients achieved a complete remission and 1 (4%) partial remission. Total cellular RNA (extracted from unselected peripheral blood mononuclear cells collected before the first cycle of treatment) was used for reverse transcription reactions using TaqMan miRNA reverse transcription kit (Applied Biosystems). As a control, we also analyzed levels of miR-101. For real-time PCR, miR-29b and miR-101 TaqMan - miRNA assays were purchased from Applied Biosystems and analyzed with TaqMan Universal PCR Master Mix (Applied Biosystems) using an Applied Biosystems Prism 7500 Sequencing detection system. The U6 small nuclear RNA was used as internal control. Expression levels of miR-29b and miR-101 from 45 patients were compared to 6 healthy donors. Expression levels of miR-29b were significantly down-regulated in patients compared to normal controls (P= 0.001) (Fig. 1A). There were no difference in terms of miR-101 expression between patients and health donors. We then compared the miR-29b and miR-101 expression levels between patients who responded to the combination therapy versus nonresponders: no differences were observed for both miR-29b and miR-101 expression (P= 0.56) (Fig.1B). Difference in baseline miR-29b expression levels. (A) Difference in baseline miR-29b expression levels between AML patients and healthy controls. (B) Difference in baseline miR-29b expression levels between responders and nonresponders. Exact P values are shown over the columns; unpaired, two-tailed t test were performed for statistical analysis. Our results fail to detect a relationship between miR-29b levels and response to 5-AZA based therapy. This difference could be explained by the relative small sample size, the source of RNA (peripheral blood versus bone marrow) and potentially the fact that miR-29b may predict for response to decitabine but not to 5-AZA in combination. In regards to the source of RNA, it should be noted that Blum et al. used unsorted bone marrow specimens whereas we used peripheral blood. The median blast percent in the blood of our patients was 6% (range 0–86%) whereas it was 35% (range 8–93%) in the bone marrow. In our experience, it is unlikely that the differences in blast percentage would explain the potential differences in gene expression levels. Despite these limitations, these results indicate that larger studies need to be performed to confirm the role of miRNAs in response to hypomethylating agent based therapy. H.Y. designed and performed research, analyzed data and wrote the manuscript; Z.F., Y.W., Y.H., G.C., and H. K. performed research, G.G.-M. designed experiment, analyzed data, wrote manuscript and funded the study. Hui Yang*, Zhihong Fang*, Yue Wei*, Yumin Hu*, George A. Calin†, Hagop M. Kantarjian*, Guillermo Garcia-Manero*, * Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, † Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas.

The Prognostic Implication of Adult Comorbidity Evaluation 27 Score in CML Patients on Tyrosine-Kinase Inhibitors

BackgroundCentral Line Associated Bloodstream Infections (CLABSIs) remain a significant medical problem for critically ill cancer patients who required catheters for extended durations. Minocycline (M) -Rifampin (R) loaded catheters have shown the greatest impact on reducing CLABSIs; however, there is a risk for developing antibiotic resistant organisms when exposed to catheters whose concentration becomes depleted below antimicrobially effective levels due to extended indwells. Chlorhexidine (CH) and M-R combination catheters (MRCH) have been proposed as a next generation catheter with improved performance. Here we studied whether bacteria that were Tetracycline and Rifampin resistant became resistant to MRCH when allowed to form biofilms on MRCH catheters depleted below antimicrobially effective MRCH concentrations.MethodsMinimum inhibitory concentrations (MICs) of Tetracycline and/or Rifampin resistant stock isolates were measured by standard microbroth dilution methods. MRCH catheters were depleted to below antimicrobially effective concentrations by soaking in serum for 6 weeks. The resistant bacteria were then allowed to form biofilm for 24 hrs on the depleted catheters in broth. Following 24 hour incubation the adherent (breakthrough) bacteria were removed by sonication and MICs were remeasured. The same organisms grown on non-antimicrobial catheters were used as controls.ResultsMICs (ug/mL) of the organisms against each agent and the combination are tabulated below:MICs (ug/mL) of the organisms against each agent and the combinationConclusionThe M and R resistant bacteria did not develop in vitro resistance to the MRCH combination after forming biofilms on MRCH catheters depleted below antimicrobially effective concentrations.DisclosuresJoel Rosenblatt, PhD, Cook Medical (Shareholder, Other Financial or Material Support, Inventor of the MRCH catheter technology which is owned by the University of Texas MD Anderson Cancer Center and has been licensed to Cook Medical)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Inventor of the MRCH catheter technology which is owned by the University of Texas MD Anderson Cancer Center and has been licensed to Cook Medical) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

A Brief History of Thoracic Surgery at the University of Texas MD Anderson Cancer Center

David J Stewart returned to Ottawa from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) in 2011 to assume the position of Head of the Division of Medical Oncology at The Ottawa Hospital and the University of Ottawa. He received his MD degree from Queen's University, Kingston, followed by training in Internal Medicine at McGill University and in medical oncology in the Department of Developmental Therapeutics at the UT MD Anderson Cancer Center. He first moved from MD Anderson to the University of Ottawa and the Cancer Care Ontario Ottawa Regional Cancer Center in 1980, and served as Chief of Medical Oncology at the Ottawa Civic Hospital from 1989 to 1999. He returned to the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center from 2003 to 2011 where he served as Chief of the Section of Experimental Therapeutics (2003–2005), Chair Ad Interim (2005), Deputy Chair (2006–2009) and Director of Translational Research (2009–2011). He was also the Principle Investigator of MD Anderson’ Phase II N01 contract with the National Cancer Institute, and was the clinical leader of a number of other federally funded translational research project. He has more than 300 peer-reviewed publications, with a research focus on Phase I and II trials of new anticancer agents, translational research and resistance to anticancer agents. He also has a major interest in and concern for issues impeding cancer clinical research, with publications that have included (among others): Cancer: the road to Amiens (J. Clin. Oncol. 27(3), 328–33 [2009]); Equipoise lost: ethics, costs and the regulation of cancer clinical research (J. Clin. Oncol. 28(17), 2925–35 [2010]); Fool's gold, lost treasures and the randomized clinical trial (BMC Cancer 13(1), 193 [2013]); and Redefining cancer: a new paradigm for better and faster treatment innovation (J. Popul. Ther. Clin. Pharmacol. 21(1), e56–e65 [2014]). His experience in both the American and Canadian healthcare systems has provided him a unique perspective on how common regulatory factors seriously impair access to effective new therapies and drive inordinately high clinical research costs in both countries.