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Kahee A. Mohammed, Leslie Hinyard, Martin W. Schoen, Christian J. Geneus, Eric S. Armbrecht, Fred R. Buckhold, and Thomas E. Burroughs

Background: This study aimed to determine patient-, tumor-, and hospital-level characteristics associated with venous thromboembolism (VTE), and to assess the impact of VTE on in-hospital mortality and length of hospital stay in hospitalized patients with metastatic cancer. Methods: Using the Nationwide Inpatient Sample database, a cross-sectional analysis was performed of patients aged ≥18 years with at least 1 diagnosis of primary solid tumor and subsequent secondary or metastatic tumor between 2008 and 2013. Results: Among 850,570 patients with metastatic cancer, 6.6% were diagnosed with VTE. A significant trend for increasing VTE rates were observed from 2008 to 2013 (5.7%–7.2%; P<.0001). Using an adjusted multilevel hierarchical regression model, higher odds of VTE were seen among women (odds ratio [OR], 1.04; 95% CI, 1.02–1.06), black versus white patients (OR, 1.14; 95% CI, 1.11–1.18), and those with an Elixhauser comorbidity index score of ≥3 (OR, 2.50; 95% CI, 2.38–2.63). Hospital-level correlates of VTE included treatment in a teaching hospital (OR, 1.05; 95% CI, 1.01–1.11) and an urban location (OR, 1.18; 95% CI, 1.09–1.27), and admission to hospitals in the Northeast (OR, 1.16; 95% CI, 1.08–1.24) and West (OR, 1.09; 95% CI, 1.03–1.16) versus the South. Patients with metastasis to the liver, brain, or respiratory organs and those with multiple (≥2) metastatic sites had higher odds of VTE, whereas those with metastasis to lymph nodes and genital organs had lower odds. Patients diagnosed with versus without VTE had higher odds of in-hospital mortality (OR, 1.50; 95% CI, 1.38–1.63) and prolonged hospital stay (OR, 1.65; 95% CI, 1.57–1.73). Conclusions: The frequency of VTE in patients with metastatic cancer is increasing. Patient characteristics, hospital factors, and site of metastasis independently predict the occurrence of VTE and allow for better stratification of patients with cancer according to their VTE risk.

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Renato G. Martins, Thomas A. D’Amico, Billy W. Loo Jr, Mary Pinder-Schenck, Hossein Borghaei, Jamie E. Chaft, Apar Kishor P. Ganti, Feng-Ming (Spring) Kong, Mark G. Kris, Inga T. Lennes, and Douglas E. Wood

Patients with stage IIIA non–small cell lung cancer, determined based on involvement of ipsilateral mediastinal lymph nodes, represent the most challenging management problem in this disease. Patients with this stage disease may have very different degrees of lymph node involvement. The pathologic confirmation of this involvement is a key step in the therapeutic decision. The difference in the degree of lymph node compromise has prognostic and treatment implications. Based on multiple considerations, patients can be treated with induction chemotherapy, chemoradiotherapy followed by surgery, or definitive chemoradiotherapy without surgery. Data derived from clinical trials have provided incomplete guidance for physicians and their patients. The best therapeutic plan is achieved through the multidisciplinary cooperation of a team specialized in lung cancer.

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Heike Reinhardt, Rainer Trittler, Alison G. Eggleton, Stefan Wöhrl, Thomas Epting, Marion Buck, Sabine Kaiser, Daniel Jonas, Justus Duyster, Manfred Jung, Martin J. Hug, and Monika Engelhardt

Background: In an interdepartmental cooperation, we investigated the feasibility and benefits of implementing dose banding of chemotherapy at our medical center. Based on this concept, chemotherapy doses are clustered into bands of similar dosage levels, thereby allowing the preproduction of frequently used standard doses of drugs, with sufficient physicochemical stability. Although established practice in the United Kingdom, there is little published evidence of its introduction elsewhere. Methods: We performed an analysis of local prescribing practice (22,310 chemotherapies) and identified gemcitabine, 5-fluorouracil, and carboplatin, among various others, as cytotoxic drugs suitable for dose banding. Results: First, we determined the physicochemical stability of the selected chemotherapy drugs during 12-weeks' storage by performing pH analysis and visual examination for color change or particles. No relevant changes were identified. Gemcitabine was selected for quantitative high-performance liquid chromatography analysis and we were able to show that ≥95% remained after 12 weeks' storage, in accordance with international guidelines. To simulate a worst case scenario, we performed microbiological stability testing of simulated cytotoxic compounding by replacing the cytotoxic drug with liquid media. Samples were incubated over defined storage time points (3, 6, and 12 weeks) and evaluated using the direct inoculation method. For the container integrity test, we deposited the samples into highly contaminated broth for 1 hour. Microbiological stability was demonstrated in both tests for the full storage period. Conclusions: Our data show that 12-weeks' storage of selected cytotoxic products is feasible from a microbiological perspective. Sterility of prepared products was maintained under extreme storage conditions. Gemcitabine content was in accordance with international guidelines after 12-weeks' storage. These results support the introduction of dose-banded gemcitabine products with the predicted advantages of optimized pharmacy workflow and reduced patient waiting times. We highlight the need for further research and consensus on the performance of purity analyses in dose-banded drug products.

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Muhamed Baljevic, Douglas W. Sborov, Ming Y. Lim, Jens Hillengass, Thomas Martin, Jorge J. Castillo, Michael B. Streiff, Shaji K. Kumar, and Natalie S. Callander

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

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Thomas Melchardt, Katharina Troppan, Lukas Weiss, Clemens Hufnagl, Daniel Neureiter, Wolfgang Tränkenschuh, Konstantin Schlick, Florian Huemer, Alexander Deutsch, Peter Neumeister, Richard Greil, Martin Pichler, and Alexander Egle

Background: Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network–International Prognostic Index (NCCN-IPI) score to determine which were the most useful. Patients and Methods: This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Results: Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. Conclusions: In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers.

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Marina Deuker, Giuseppe Rosiello, Lara Franziska Stolzenbach, Thomas Martin, Claudia Collà Ruvolo, Luigi Nocera, Zhe Tian, Frederik C. Roos, Andreas Becker, Luis A. Kluth, Derya Tilki, Shahrokh F. Shariat, Fred Saad, Felix K.H. Chun, and Pierre I. Karakiewicz

Background: The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. Materials and Methods: Within the Nationwide Inpatient Sample database (2000–2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64–72, 73–79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. Results: Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). Conclusions: Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.

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Shaji K. Kumar, Natalie S. Callander, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jason C. Chandler, Caitlin Costello, Matthew Faiman, Henry C. Fung, Cristina Gasparetto, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Adetola Kassim, Michaela Liedtke, Thomas Martin, James Omel, Noopur Raje, Frederic J. Reu, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Steven P. Treon, Donna Weber, Joachim Yahalom, Dorothy A. Shead, and Rashmi Kumar

Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article.

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George D. Demetri, Scott Antonia, Robert S. Benjamin, Marilyn M. Bui, Ephraim S. Casper, Ernest U. Conrad III, Thomas F. DeLaney, Kristen N. Ganjoo, Martin J. Heslin, Raymond J. Hutchinson, John M. Kane III, G. Douglas Letson, Sean V. McGarry, Richard J. O'Donnell, I. Benjamin Paz, John D. Pfeifer, Raphael E. Pollock, R. Lor Randall, Richard F. Riedel, Karen D. Schupak, Herbert S. Schwartz, Katherine Thornton, Margaret von Mehren, and Jeffrey Wayne

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Matthew H. Kulke, Manisha H. Shah, Al B. Benson III, Emily Bergsland, Jordan D. Berlin, Lawrence S. Blaszkowsky, Lyska Emerson, Paul F. Engstrom, Paul Fanta, Thomas Giordano, Whitney S. Goldner, Thorvardur R. Halfdanarson, Martin J. Heslin, Fouad Kandeel, Pamela L. Kunz, Boris W. Kuvshinoff II, Christopher Lieu, Jeffrey F. Moley, Gitonga Munene, Venu G. Pillarisetty, Leonard Saltz, Julie Ann Sosa, Jonathan R. Strosberg, Jean-Nicolas Vauthey, Christopher Wolfgang, James C. Yao, Jennifer Burns, and Deborah Freedman-Cass

Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus.

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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Thomas J. Dilling, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Steven Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.