bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvage or Adjuvant Radiation Therapy: Counseling Patients on the Benefits
Authors: Nielsen Matthew E. , Trock Bruce J. , Walsh Patrick C.
Published: April 2017

Recent developments in the urologic oncology literature suggest that residual local disease—as opposed to the presence of occult metastases at surgery—may characterize a more substantial component of the natural history of the recurrence and progression of initially clinically localized prostate cancer than previously appreciated. These important studies have illuminated the extent to which postoperative radiotherapy (RT) may provide benefit to patients with adverse pathologic features (extraprostatic extension, seminal vesicle invasion, or positive surgical margins) or biochemical recurrence after radical prostatectomy. Nevertheless, the question of whether all patients with the aforementioned adverse features should undergo immediate adjuvant RT versus initial observation with more selective—but early—salvage RT in the event of biochemical failure remains the subject of heated controversy. This article reviews salient recent studies in this field to address important questions relevant to counseling patients on the use of postprostatectomy RT. Discussion points include data supporting benefit (efficacy), questions of generalizability of benefit (effectiveness) and risks, and important questions for further study.
The Role of Hematopoietic Stem Cell Transplant in Follicular Lymphoma
Authors: Faber Edward A. , Vose Julie M.
Published: April 2017

Substantial progress has been made in the clinical management of patients with follicular lymphoma over the past 2 decades. However, the role of autologous and allogeneic stem cell transplantation in these patients remains controversial. Myeloablative chemotherapy or radioimmunotherapy supported by autologous hematopoietic cell transplantation has been shown to lead to a longer progression-free survival and, in some studies, improved survival over standard therapy. However, in the era of rituximab-based therapies used as part of induction or salvage, these historical trials may not be representative. Allogeneic stem cell transplantation offers the advantages of a tumor-free graft and some immunologic graft-versus-lymphoma effects. However, fully myeloablative transplants have high morbidity and mortality rates. Dose-reduced conditioning regimens followed by allogeneic hematopoietic cell transplantation have substantially reduced treatment-related mortality and perhaps will produce better outcomes long-term. This article outlines some historical information regarding stem cell transplantation for follicular lymphoma and discusses recent modifications that may improve outcomes, such as adding radioimmunotherapy to autologous stem cell transplantation or using alternative dose-reduced regimens that could benefit patients with reduced toxicities.
An Update on the Role of Interim Restaging FDG-PET in Patients With Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma
Authors: Moskowitz Craig H. , Zelenetz Andrew , Schoder Heiko
Published: April 2017

A significant amount of literature is available on treatment monitoring and response assessment in lymphoma using FDG-PET, yet confusion exists concerning the potential and limitations of FDG-PET for determining the presence of residual disease during chemotherapy (interim FDG-PET). This article reviews the role of interim FDG-PET in 3 important scenarios: untreated diffuse large B-cell lymphoma, untreated Hodgkin lymphoma, and relapsed or refractory aggressive lymphoma in transplant-eligible patients, and provides recommendations on the use of this imaging modality in these settings.
Genomic Analysis of Lymphoma: Potential for Clinical Application
Authors: Chan Wing C. , Armitage James O.
Published: April 2017

The application of gene expression profiling to the study of lymphomas will significantly influence the way these tumors are diagnosed and treated. Diffuse large B-cell lymphoma is now known to consist of several different genetic entities with different clinical presentations and therapeutic outcomes. In both follicular and diffuse large B-cell lymphoma, these studies have shown that host–tumor interactions have a major impact on the clinical course. Findings of gene expression profiling in diffuse large B-cell lymphoma has indicated the frequent up-regulation of the nuclear factor-κB and B-cell receptor signaling pathways in the activated B-cell type. Drugs targeting these pathways may be effective in the treatment of these cases and clinical trials have been initiated based on these findings. Gene expression profiling may assist in the selection of treatments based on specific metabolic pathways shown to be active in a particular lymphoma. These techniques offer the promise of truly personalized medicine for patients with lymphoma.
Advancements in Radiation Techniques for Gastric Cancer
Authors: Callister Matthew D. , Gunderson Leonard L.
Published: April 2017

All but the earliest cases of nonmetastatic gastric cancer represent a therapeutic challenge given the high propensity of these patients to develop locoregional and distant relapse. Neoadjuvant or adjuvant strategies that include chemoradiotherapy or chemotherapy have been associated with significant toxicity, but also improvement in patient survival. Technologic advances in the planning and delivery of radiotherapy (RT) have enabled significant progress in the accuracy and conformality of radiation treatment. Four-dimensional CT and image-guided RT improve the accuracy of radiation treatment. Three-dimensional RT and intensity-modulated RT allow increased conformality of radiation dose distribution, sparing of normal organs, and providing opportunity for dose escalation. Initial clinical experience with these technologies shows favorable tolerance and outcomes.
Short Screening Tools for Cancer-Related Distress: A Review and Diagnostic Validity Meta-Analysis
Authors: Mitchell Alex J.
Published: April 2017

Clinicians are increasingly seeking efficient methods to identify distress in cancer settings, using short screening tools with fewer than 14 items that take less than 5 minutes to complete. This article examines the value of these tools for identifying cancer-related distress, defined by semi-structured interview. An updated search, appraisal, and meta-analysis, with adjustments made for heterogeneity and underlying prevalence variations, identified 45 potentially useful short and ultra-short tools, although most were intended to help diagnose depression, with few targeted at distress (or anxiety). Very few studies attempted robust validation in cancer settings. When studies were limited to those tested against distress defined by semi-structured interview, only 6 methods had been validated, namely the Hospital Anxiety and Depression Scale (HADS; 13 studies, 14 items), the Distress Thermometer (DT; 4 studies, 1 item), a single verbal question (4 studies, 1 item), the Psychological Distress Inventory (PDI; 1 study, 13 items), combined DT and an impact thermometer (1 study, 2 items), and combined 2 verbal questions (1 study, 2 items). Comparing these 6 approaches side-by-side suggests that for screening, all tools have approximately the same accuracy. Therefore, choice of a short screening tool for distress can be based on acceptability or cost-effectiveness. Here, best evidence supports use of the DT or single verbal question. Remarkably, the overall accuracy of these single-item approaches seems comparable to that of the 14-item HADS (total score), whereas their efficiency is superior. For case-finding, data are sparse but no method seems to be entirely satisfactory. Current evidence suggests that the optimal short methods for identifying distress are 2 verbal questions or PDI. Of these approaches, the 2 verbal questions has superior efficiency. All short methods may be augmented by repeated application, an assessment of unmet needs (problem list), and clarification regarding the need for professional help. No screening tool should be seen as an alternative to careful clinical assessment and management. Despite much interest in the development of short and ultra-short tools, data on validation and implementation are currently incomplete. Nevertheless, short methods seem to be at least as successful as the HADS, although substantially more efficient and hence more acceptable, and therefore may be a suitable initial method of assessment in busy clinical settings.
The Role of Radiation Therapy in the Treatment of Medullary Thyroid Cancer
Authors: Terezakis Stephanie A. , Lee Nancy Y.
Published: April 2017

Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from parafollicular or C cells of the thyroid gland. Surgical resection is the mainstay of treatment for MTC. External-beam radiation treatment (EBRT) has traditionally played a limited role in the management of MTC. Despite aggressive surgery, patients at high risk for local recurrence may benefit from adjuvant EBRT. With improvements in radiation technique, adequate dose can be effectively delivered to the region at risk while minimizing dose to surrounding critical structures. Although the role of EBRT in the management of these tumors has thus far been poorly defined, EBRT should be considered as a treatment option for patients with locally advanced MTC to optimize locoregional control.
Extending Comprehensive Cancer Center Expertise in Clinical Cancer Genetics and Genomics to Diverse Communities: The Power of Partnership
Authors: MacDonald Deborah J. , Blazer Kathleen R. , Weitzel Jeffrey N.
Published: April 2017

Rapidly evolving genetic and genomic technologies for genetic cancer risk assessment (GCRA) are revolutionizing the approach to targeted therapy and cancer screening and prevention, heralding the era of personalized medicine. Although many academic medical centers provide GCRA services, most people receive their medical care in the community setting. However, few community clinicians have the knowledge or time needed to adequately select, apply, and interpret genetic/genomic tests. This article describes alternative approaches to the delivery of GCRA services, profiling the City of Hope Cancer Screening & Prevention Program Network (CSPPN) academic and community-based health center partnership as a model for the delivery of the highest-quality evidence-based GCRA services while promoting research participation in the community setting. Growth of the CSPPN was enabled by information technology, with videoconferencing for telemedicine and Web conferencing for remote participation in interdisciplinary genetics tumor boards. Grant support facilitated the establishment of an underserved minority outreach clinic in the regional County hospital. Innovative clinician education, technology, and collaboration are powerful tools to extend GCRA expertise from a National Cancer Institute–designated Comprehensive Cancer Center, enabling diffusion of evidenced-base genetic/genomic information and best practice into the community setting.
Specific Targets in Sarcoma and Developmental Therapeutics
Authors: Thomas David M. , Wagner Andrew J.
Published: April 2017

Connective tissue tumors comprise a rich array of subtypes, many of which possess strong pathognomonic phenotypes and genotypes of therapeutic significance. This article describes recent applications of targeted and nontargeted therapeutic agents in connective tissue tumors that illustrate important themes in drug development. Targeted therapy has exploited the paradigms of oncogene and lineage addiction. In other cases, potential targets are more difficult to classify, such as the role of the insulin-like growth factor 1 pathway in Ewing's sarcoma. Understanding why these pathways seem critical in some cancers, and in some individuals but not others, is important in identifying novel therapeutic opportunities in an age of personalized medicine.
Maintenance Chemotherapy in Non–Small Cell Lung Cancer
Authors: Eaton Keith D. , Martins Renato G.
Published: April 2017

Recent trials have shown a benefit with maintenance therapy after 4 to 6 cycles of chemotherapy. These trials have shown improvement in progression-free survival using agents approved as second-line therapy in non-small cell lung cancer. Trials using erlotinib and pemetrexed showed improvement in overall survival. Consideration of trial design is critical for the interpretation of these results. Data on quality of life and cost have not been presented, but will ultimately be important in evaluating the usefulness of these approaches.
Review of the Role of Opioids in Cancer Pain
Authors: Trescot Andrea M.
Published: April 2017

Cancer pain is unfortunately very prevalent, with opioids the mainstay of treatment. Knowledge of the types of pain caused by cancer and the effects of various opioids would be expected to improve pain therapy. This article addresses the use, side effects, formulations, and metabolism of the most commonly used opioids in cancer pain management, including morphine, codeine, hydrocodone, hydromorphone, fentanyl, and methadone. The role of opioid conversion and equipotent dosing when changing from one opioid to another is also described.
Chronic Pain Management in Cancer Survivors
Authors: Moryl Natalie , Coyle Nessa , Essandoh Samuel , Glare Paul
Published: April 2017

The problem of pain in cancer survivors is attracting increased attention. Although comprehensive information about the prevalence of persistent pain in the cancer survivor population is currently lacking, it is known to depend on the type of cancer, comorbid conditions, and the initial pain management. Epidemiologic studies generally categorize pain in patients with cancer as either pain directly caused by the neoplastic process or related phenomena, pain occurring as a complication of anticancer treatment, or pain unrelated to the neoplastic process, caused by debility or concurrent disorders. This article focuses on pain syndromes in cancer survivors and the safe use of opioid therapy in this population when its ongoing use is part of the pain management plan. The use of physical therapy, rehabilitation therapy, and cognitive behavioral therapy, which are all extremely important aspects of pain management in the cancer survivor, are briefly mentioned.
Mammographic Breast Density: Effect on Imaging and Breast Cancer Risk
Authors: Pinsky Renee W. , Helvie Mark A.
Published: April 2017

Mammographic breast density has been studied for more than 30 years. Greater breast density not only is related to decreased sensitivity of mammograms because of a masking effect but also is a major independent risk factor for breast cancer. This article defines breast density and reviews literature on quantification of mammographic density that is key to future clinical and research protocols. Important influences on breast density are addressed, including age, menopausal status, exogenous hormones, and genetics of density. Young women with dense breasts benefit from digital mammographic technique. The potential use of supplemental MRI and ultrasound screening techniques in high-risk women and women with dense breasts is explored, as are potential risk reduction strategies.
Initial Management and Follow-up of Differentiated Thyroid Cancer in Children
Authors: Waguespack Steven G. , Francis Gary
Published: April 2017

Children with differentiated thyroid cancer (DTC) often present with metastatic disease and have a high risk for recurrence, but rarely die of the disease. This article reviews DTC in children and discusses current approaches to their initial care and follow-up. These recommendations take into account the greater risk for recurrence and lower disease-specific mortality in these patients. Total thyroidectomy and central compartment lymph node dissection are appropriate for most children, but should be performed by a high-volume thyroid surgeon. Radioactive iodine (RAI) should generally be prescribed for those at very high risk for recurrence or known to have microscopic residual disease, and those with iodine-avid distant metastases. RAI should be considered in other patients only after carefully weighing the relative risks and benefits and the aggressiveness of the clinical presentation, because RAI may be associated with an increased risk for second malignancies and an increase in overall morbidity and mortality. All patients should be treated with thyroid hormone suppression, and follow-up should be lifelong. However, the degree of thyroid hormone suppression and frequency of disease surveillance usually decrease over time as patients are determined to be disease-free.
The Biologic Spectrum of Thymic Epithelial Neoplasms: Current Status and Future Prospects
Authors: Cheney Richard T.
Published: April 2017

Thymoma is the most common anterior mediastinal tumor in adults and is frequently associated with autoimmune disorders such as myasthenia gravis. Thymomas are a diverse group of epithelial neoplasms with a behavioral spectrum that spans the complete clinical gamut from entirely benign to highly aggressive, lethal thymic carcinomas. The biologic behavior seems to depend primarily on the clinical stage at presentation and histologic subtype. This article discusses thymic organogenesis, Masaoka staging, WHO histologic classification of thymoma and thymic carcinoma, and selected molecular characteristics that highlight this diversity. This discussion will further underscore both the similarities and differences between categories of thymic epithelial neoplasms and offer support for the notion that tumor heterogeneity and/or tumor progression may explain the observed clinical variation in behavior. Recommendations are offered for future investigational approaches to further the understanding of the complexity of these tumors.
NCCN Task Force Report: Specialty Pharmacy
Authors: Schwartz Rowena N. , Eng Kirby J. , Frieze Deborah A. , Gosselin Tracy K. , Griffith Niesha , Seung Amy Hatfield , Hinkel Jennifer M. , Johnson Philip E. , Johnson Shirley A. , Li Edward C. , Szabatura Audrea Hotsko , Wong Michael K.
Published: April 2017

The use of specialty pharmacies is expanding in oncology pharmacy practice. Specialty pharmacies provide a channel for distributing drugs that, from the payor perspective, creates economies of scale and streamlines the delivery of expensive drugs. Proposed goals of specialty pharmacy include optimization of pharmaceutical care outcomes through ensuring appropriate medication use and maximizing adherence, and optimization of economic outcomes through avoiding unwarranted drug expenditure. In oncology practice, specialty pharmacies have become a distribution channel for various agents. The use of a specialty pharmacy, and the addition of the pharmacist from the specialty pharmacy to the health care team, may not only provide benefits for care but also present challenges in oncology practice. The NCCN Specialty Pharmacy Task Force met to identify and examine the impact of specialty pharmacy practice on the care of people with cancer, and to provide recommendations regarding issues discussed. This report provides recommendations within the following categories: education and training of specialty pharmacy practitioners who care for individuals with cancer, coordination of care, and patient safety. Areas for further evaluation are also identified.
Insights and Perspectives in the Clinical and Operational Management of Cancer-Related Anemia
Authors: Hinkel Jennifer M. , Li Edward C. , Sherman Stephen L.
Published: April 2017

Management of anemia in patients with cancer presents challenges from clinical, operational, and economic perspectives. Clinically, anemia in these patients may result from treatment (chemotherapy, radiation therapy, or surgical interventions) or from the malignancy itself. Anemia not only contributes to cancer-related fatigue and other quality of life issues, but also affects prognosis. From the operational perspective, a patient with cancer who is also anemic may consume more laboratory, pharmacy, and clinical resources than other patients with cancer.
The Role of Iron Chelation Therapy for Patients With Myelodysplastic Syndromes
Authors: Steensma David P.
Published: April 2017

The appropriate role of iron chelation therapy in the management of patients with myelodysplastic syndromes (MDS) is currently controversial. Some investigators interpret data to indicate that careful attention to iron parameters, with early initiation of iron chelation in patients with evidence suggesting transfusion-associated iron overload, is an important component of high-quality MDS patient care. Other physicians are more skeptical, noting that chelation can be cumbersome or costly, has associated risks, and has not yet been shown to reduce morbidity or mortality in the MDS setting. This article reviews the extent to which iron chelation therapy might be either an important clinical intervention in MDS or a distraction from more pressing clinical concerns.
Point: Chemosensitivity Assays Have a Role in the Management of Recurrent Ovarian Cancer
Authors: Schink Julian C. , Copeland Larry J.
Published: April 2017

In this era of personalized medicine, patients with recurrent ovarian cancer deserve better than the 25% response rate that is associated with drugs selected based on clinical information alone. In the past decade, marked laboratory improvements have enabled chemosensitivity assay testing to yield a 0.70 correlation with response, and to accurately predict progression-free and overall survival. Compelling retrospective data supporting the use of this technology cannot be ignored while waiting for a cooperative group to test whether chemosensitivity assay should be used to direct salvage therapy.
Counterpoint: Chemosensitivity Assays for Recurrent Ovarian Cancer
Authors: Markman Maurie
Published: April 2017

Unfortunately, no reliable evidence-based data have shown any in vitro chemosensitivity assay strategy to be clinically useful in the management of recurrent ovarian cancer, despite frequent use. Several clinical trials have been proposed with the potential to support or refute the relevance of these approaches.
Trastuzumab-Related Cardiac Dysfunction
Authors: Telli Melinda L. , Witteles Ronald M.
Published: April 2017

The use of trastuzumab in the adjuvant and metastatic treatment of breast cancer is associated with both symptomatic and asymptomatic cardiotoxicity. The long-term significance of these events, isolating known cardiotoxic effects of anthracyclines from those of trastuzumab, and the appropriateness of referring to trastuzumab-related cardiotoxicity as reversible rather than responsive to trastuzumab withdrawal and heart failure medical therapy, are issues that continue to be debated. This article provides an overview of the available cardiac safety data from the major trastuzumab clinical trials in breast cancer, highlighting areas of ongoing controversy. Important recent data documenting the occurrence and prognostic use of cardiac troponin I elevations among patients treated with trastuzumab are placed into context with the mechanistic insight these data provide and the implications for clinical practice today.
Does Use of the Adjuvant! Model Influence Use of Adjuvant Therapy Through Better Risk Communication?
Authors: Belkora Jeffrey K. , Hutton David W. , Moore Dan H. , Siminoff Laura A.
Published: April 2017

Adjuvant! is a model that provides recurrence and mortality risk predictions for patients with breast cancer considering adjuvant therapies. Although low-risk patients who saw Adjuvant! chose adjuvant therapy less frequently, whether this was because of educational or other aspects of the decision aid is unknown. The authors explored whether Adjuvant! affects choice of therapy through increased patient knowledge. A subset of data were analyzed from a cluster randomized trial in which oncology practices in 2 major United States cities were randomly assigned to use either Adjuvant! or an informational pamphlet to educate patients. Of 405 patients, 48 were low-risk, with 28 assigned to the decision aid and 20 to the pamphlet. Among the low-risk patients, using frequency tables and Fisher exact tests, the authors explored whether Adjuvant! was associated with more accurate patient estimates of survival; whether accuracy was associated with treatment choice; and whether, after controlling for accuracy, any remaining association was seen between Adjuvant! and treatment choice. Adjuvant! was associated with more accurate estimates of baseline prognosis compared with the pamphlet (57% vs. 25%; P = .04). Patients who had more accurate estimates of baseline prognosis were less likely to choose adjuvant therapy (62% vs. 89%; P = .04). After controlling for accuracy, no statistically significant association was found between the use of Adjuvant! and adjuvant therapy (P = .59 and P = .11 for inaccurate and accurate patients, respectively). Adjuvant! seems to influence patient choice through educational rather than other means of persuasion. However, many patients held inaccurate risk perceptions after viewing Adjuvant!.
Heparin-Induced Thrombocytopenia in Cancer
Authors: Miriovsky Benjamin J. , Ortel Thomas L.
Published: April 2017

Heparin-induced thrombocytopenia is a common and clinically important drug-induced complication that can cause life- and limbthreatening thrombosis. Epidemiologically, the disease has been studied in many different clinical settings, but little is known about it in cancer patients, a population at increased risk for thrombosis and thus exposure to heparin products. Additionally, thrombocytopenia is a common finding in cancer patients. The convergence of these variables highlights the importance of an increased understanding of the disease in cancer patients.
Risk Assessment and Prophylaxis for VTE in Cancer Patients
Authors: Khorana Alok A.
Published: April 2017

The frequency of venous thromboembolism (VTE) is rising in patients with cancer. VTE contributes to mortality and morbidity, but the risk for VTE can vary widely between individual patients. Clinical risk factors for VTE in cancer include primary site of cancer, use of systemic therapy, surgery, and hospitalization. Biomarkers predictive of VTE include platelet and leukocyte counts, hemoglobin, D-dimer, and tissue factor. A recently validated risk model incorporates 5 easily available variables and can be used clinically to identify patients at increased risk of VTE. In high-risk settings, including surgery and hospitalization, thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins has been shown to be safe and effective. Recent studies have also suggested a potential benefit for thromboprophylaxis in the ambulatory setting, although criteria for selecting patients for prophylaxis are not currently well defined. This article focuses on recent and ongoing studies of risk assessment and prophylaxis in patients with cancer.
Endoscopic Therapy of Esophageal Premalignancy and Early Malignancy
Authors: Nealis Thomas B. , Washington Kay , Keswani Rajesh N.
Published: April 2017

Esophageal adenocarcinoma (EAC) is an often deadly cancer with a rising incidence in Western countries. Chronic gastroesophageal reflux disease is associated with the metaplastic transformation of normal squamous epithelium to premalignant specialized intestinal metaplasia within the esophagus (Barrett's esophagus). Barrett's esophagus may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), or even EAC. Although nondysplastic Barrett's esophagus progresses to EAC at a rate of 0.5% per year, rates of progression for true LGD and HGD are significantly higher. Treatment is mandatory for HGD and may be appropriate in select patients with nondysplastic Barrett's esophagus and many with LGD. Thus, accurate pathologic assessment is necessary before considering endoscopic therapy. Previously, only esophagectomy was offered to patients with HGD or EAC. However, esophagectomy has significant morbidity and mortality, and therefore endoscopic therapies have been advocated for early Barrett's neoplasia. These methods include endoscopic mucosal resection (EMR) and ablative techniques. Ablation techniques include argon plasma coagulation, multipolar electrocoagulation, laser therapy, photodynamic therapy, radiofrequency ablation, and cryotherapy. Of these, radiofrequency ablation has experienced the greatest adoption for the treatment of dysplastic Barrett's esophagus because of excellent published outcomes. The use of EMR to resect suspicious areas or raised lesions is mandatory to provide histology. In contrast, ablation techniques such as radiofrequency ablation have been shown to effectively eradicate large areas of dysplastic tissue with relative ease but do not allow for histologic assessment of the treated area. Combination EMR with radiofrequency ablation is thus advocated to resect visible lesions via EMR (providing histology) and ablate the remainder of the Barrett's esophagus. As always, the appropriate treatment is best determined after careful discussion with patients in a multidisciplinary environment. However, endoscopic therapy offers an attractive alternative to esophagectomy for early Barrett's neoplasia.
Biosimilars: Are They Ready for Primetime in the United States?
Authors: Hirsch Bradford R. , Lyman Gary H.
Published: April 2017

The introduction of alternative versions of biologic products, also known as biosimilars, into the United States market has been gaining increasing visibility as patents for many agents are nearing expiration. Unlike generics, which are regulated under the Hatch-Waxman legislation passed in 1984, the approval process for biosimilars in the United States has not been defined. In 2004, the European Union established a regulatory pathway for these agents, and the FDA is now following suit. The economic implications are large, with $66.9 billion spent on the top 20 biologics in 2009. Of the top 10 biologics, 6 are routinely used in oncology. As the regulatory requirements are debated, several critical issues must be resolved. The most obvious is that the agents must be shown to be comparable to the original biologic they intend to replace. Knowledge of pharmacokinetic parameters alone will not be adequate, but the amount of clinical data required by the FDA remains unclear. The regulations will define the ease with which a biosimilar can be brought to market, and the associated costs of trials will influence the ultimate price of the medications. Balancing the needs of the relevant stakeholders is critical to ensure patient safety while controlling costs, improving access, and encouraging innovation. This is not an easy balance to strike.
Long-Term Outcomes of Myeloid Growth Factor Treatment
Authors: Lyman Gary H. , Dale David C.
Published: April 2017

Myeloid growth factors are used to reduce myelotoxicity and the risk of infection after cancer chemotherapy and in patients with chronic neutropenia. This article addresses the long-term benefits and risks associated with granulocyte colony-stimulating factor (G-CSF) therapy in both settings. A systematic review of randomized controlled trials recently reported long-term outcomes regarding the risk of second malignancies and overall survival. Based on these studies, the risk for acute myeloid leukemia (AML) associated with known carcinogenic agents, such as chemotherapy, could not be distinguished from any risk associated with growth factor support. However, the enhanced delivery of chemotherapy dose intensity enabled by the use of G-CSF in these studies was associated with a significant reduction in all-cause mortality. Although some reduction in treatment-related mortality with G-CSF support may occur, the observed improvement in long-term survival likely relates to better disease control with more-intense G-CSF–supported chemotherapy. Myeloid growth factors have also been shown to benefit patients with severe chronic neutropenia. Almost all patients with cyclic, congenital, or idiopathic neutropenia experience response to G-CSFs. Treatment is titrated to determine a dose that provides a safe elevation in neutrophil counts. Reports have shown that patients can be maintained for years at the same dose after adjusting for growth and development. In congenital neutropenia, the inherent risk of developing myelodysplastic syndromes or AML requires careful monitoring, including routine blood counts and annual bone marrow examinations.
Evolution of Radiation Therapy Within the German Hodgkin Study Group Trials
Authors: Eich Hans Theodor , Kriz Jan , Müller Rolf-Peter
Published: April 2017

Since its beginning, more than 16,000 patients have been enrolled in the multicentric randomized trials of the German Hodgkin Study Group (GHSG) for adult patients. Within 6 study generations, the treatment of Hodgkin lymphoma has been developed stepwise by using the results of the completed protocols. Now the sixth generation is active. According to the role of radiotherapy, the study group successfully evaluated different dose–effect relationships and could also prove the efficacy of involved-field radiotherapy in early stages in combination with effective chemotherapy. Currently, a radiation dose of 20 Gy to the involved field after a mildly aggressive chemotherapy (2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD]) should be the standard for early-favorable stages according to the GHSG classification. In early-unfavorable or intermediate-risk stages, involved-field radiation therapy with 30 Gy is sufficient; the optimal chemotherapy has to be fixed. For the advanced stages, the question of radiotherapy is still unclear. Preliminary results of the GHSG and others show that additive radiotherapy after intensive chemotherapy might be useful for elective subgroups of patients. The extensive radiotherapy quality assurance program, performed by the GHSG and its radiotherapy reference center, has proven to be successful and necessary to ensure that, with reduced radiation doses and reduced radiation volumes, precise radiotherapy, as defined by the protocol, will be performed by the participating radiotherapy departments.
Evolving Paradigms in the Treatment of Newly Diagnosed Multiple Myeloma
Authors: Larocca Alessandra , Palumbo Antonio
Published: April 2017

The treatment of multiple myeloma has undergone significant changes in the past few years. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, has dramatically improved the outcome of this disease and considerably increased the treatment options available. Several trials have shown the advantages linked to the use of novel agents both in young patients, who are considered eligible for transplantation, and elderly patients, for whom a conventional therapy should be considered. These novel agents may increase the efficacy of autologous stem cell transplantation with deeper and long-lasting response. In the transplant setting, different novel agent combinations have proved to be superior to the traditional vincristine-doxorubicin-dexamethasone. Similarly, novel agents have also changed the treatment paradigm of patients not eligible for transplantation, thus replacing the traditional melphalan-prednisone approach. Preliminary data also support the role of consolidation and maintenance therapy to further improve outcomes. This article provides an overview of the latest strategies, including novel agents used to treat patients with multiple myeloma, both in the transplant and nontransplant settings.
Management of Relapsed and Relapsed/Refractory Multiple Myeloma
Authors: Laubach Jacob P. , Mitsiades Constantine S. , Mahindra Anuj , Luskin Marlise R. , Rosenblatt Jacalyn , Ghobrial Irene M. , Schlossman Robert L. , Avigan David , Raje Noopur , Munshi Nikhil C. , Anderson Kenneth C. , Richardson Paul G.
Published: April 2017

Despite significant progress in the treatment of multiple myeloma (MM) over the past decade, this disease remains incurable and almost all patients ultimately experience relapse and become refractory to treatment over time. However, the outlook for patients with relapsed MM has improved markedly with the use of the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Moreover, the development of new drug classes based on preclinical rationale and the introduction of next-generation agents is likely to further expand treatment options and improve outcomes for relapsed MM.
Developing a Referral System for Fertility Preservation Among Patients With Newly Diagnosed Cancer
Authors: Quinn Gwendolyn P. , Vadaparampil Susan T. , Gwede Clement K. , Reinecke Joyce D. , Mason Tina M. , Silva Celso
Published: April 2017

The goal of this project was to develop a referral system to increase the likelihood that patients of childbearing age with newly diagnosed cancer receive timely information about fertility, and reduce the burden oncologists may feel when discussing and exploring fertility preservation options with their patients. The group developed and examined the effectiveness of a fertility preservation referral system through pilot-testing a developed patient education brochure. During the 12-month pilot-testing period, 776 patients of childbearing age (< 40 years) were seen at H. Lee Moffitt Cancer Center and 349 brochures were taken. The reproductive endocrinologist/infertility clinic experienced a 9-fold increase in the number of calls received during the 12-month study period, with 122 calls received compared with 13 the prior year. The large increase in calls illuminates the gap in patient interest and referral, and shows an effective method to transmit this information. Improving the communication of time-sensitive information about fertility and preservation options to patients with cancer is associated with an increased likelihood of improving quality of life, reducing patient distress, and increasing use of ancillary fertility-related health services. Through referring and providing patient information, this referral system allows oncologists to fulfill their obligation and make informed decisions about fertility preservation, thereby improving the full cancer care continuum.
Creating an Effort Tracking Tool to Improve Therapeutic Cancer Clinical Trials Workload Management and Budgeting
Authors: James Pam , Bebee Patty , Beekman Linda , Browning David , Innes Mathew , Kain Jeannie , Royce-Westcott Theresa , Waldinger Marcy
Published: April 2017

Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.
Crizotinib and Testing for ALK
Authors: Shaw Alice T. , Solomon Benjamin , Kenudson Mari Mino
Published: April 2017

Crizotinib was recently approved by the US FDA for the treatment of advanced non–small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement. To ensure identification of patients most likely to benefit, the FDA approved crizotinib concurrently with a companion diagnostic test—the Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically validated, the assay can be technically challenging and costly. Therefore, other diagnostic modalities are being explored, including immunohistochemistry (IHC) and reverse transcriptase–polymerase chain reaction. This article provides an overview of the diagnostic assays available for detecting ALK rearrangement. Each assay, including ALK FISH, has its strengths and weaknesses. Recent work with commercially available ALK antibodies suggests that IHC-based tests may represent a reliable and cost-effective screening strategy; however, large multicenter studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH remains the current standard for diagnosing ALK positivity, large-scale screening of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may require development and validation of alternative screening strategies, such as combination IHC and FISH.
Effort Tracking Metrics Provide Data for Optimal Budgeting and Workload Management in Therapeutic Cancer Clinical Trials
Authors: James Pam , Bebee Patricia , Beekman Linda , Browning David , Innes Mathew , Kain Jeannie , Westcott Theresa Royce , Waldinger Marcy
Published: April 2017

Clinical trials operations struggle to achieve optimal distribution of workload in a dynamic data management and regulatory environment, and to achieve adequate cost recovery for personnel costs. The University of Michigan Comprehensive Cancer Center developed and implemented an effort tracking application to quantify data management and regulatory workload to more effectively assess and allocate work while improving charge capture. Staff recorded how much time they spend each day performing specific study-related and general office tasks. Aggregated data on staff use of the application from 2006 through 2009 were analyzed to gain a better understanding of what trial characteristics require the most data management and regulatory effort. Analysis revealed 4 major determinants of staff effort: 1) study volume (actual accrual), 2) study accrual rate, 3) study enrollment status, and 4) study sponsor type. Effort tracking also confirms that trials that accrued at a faster rate used fewer resources on a per-patient basis than slow-accruing trials. In general, industry-sponsored trials required the most data management and regulatory support, outweighing other sponsor types. Although it is widely assumed that most data management efforts are expended while a trial is actively accruing, the authors learned that 25% to 30% of a data manager's effort is expended while the study is either not yet open or closed to enrollment. Through the use of a data-driven effort tracking tool, clinical research operations can more efficiently allocate workload and ensure that study budgets are negotiated to adequately cover study-related expenses.
Management of Neuroendocrine Tumors of Unknown Origin
Authors: Polish Ariel , Vergo Maxwell T. , Agulnik Mark
Published: April 2017

Neuroendocrine tumors (NETs) of unknown origin account for more than 10% of all NETs. Most of these tumors are poorly differentiated and, thus, very aggressive. Establishing the location of the primary tumor can be challenging. Workup of these NETs of unknown origin includes a thorough family history, immunohistochemistry, imaging, and OctreoScan. If the location of the primary malignancy is not determined, treatment is often initiated based on the grade and level of differentiation of the tumor, with well- and moderately differentiated tumors treated as carcinoid tumors, whereas poorly differentiated tumors are treated similarly to small cell tumors. Therapy is chosen based on symptoms and with the goal of debulking tumor when feasible and safe.
Carcinoma of Unknown Primary: Focused Evaluation
Authors: Varadhachary Gauri R.
Published: April 2017

The management of carcinoma of unknown primary (CUP) has evolved over the past decade, with the advent of sophisticated imaging and pathologic tests. Especially in the era of tailored therapeutics, this presents both an opportunity and a challenge. For the initial workup of a patient with CUP, a focused search for the primary cancer based on clinical presentation is recommended. Exhaustive use of unnecessary imaging, invasive studies, and pathologic tests adds to patient discomfort, is associated with significant cost, and often has a low yield for detection of a primary cancer. Physicians should be able to justify the need for ancillary tests and how results may impact the comprehensive management of patients. Over the next several years, physicians also need to focus their efforts on refining CUP subsets (e.g., isolated nodal, osseous, carcinomatosis presentations) and leveraging selective genomics and proteomics techniques to eventually deliver validated new therapeutic approaches to patients. This will require creative approaches to clinical studies, including establishment of international CUP cooperative groups and innovative designs. Just as physicians need to be selective in their diagnostic approach, they also need to be selective in their research efforts as they continue to impact quality of life and survival for patients with CUP.
NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia
Authors: O'Brien Susan , Berman Ellin , Moore Joseph O. , Pinilla-Ibarz Javier , Radich Jerald P. , Shami Paul J. , Smith B. Douglas , Snyder David S. , Sundar Hema M. , Talpaz Moshe , Wetzler Meir
Published: April 2017

The advent of imatinib has dramatically improved outcomes in patients with chronic myelogenous leukemia (CML). It has become the standard of care for all patients with newly diagnosed chronic-phase CML based on its successful induction of durable responses in most patients. However, its use is complicated by the development of resistance in some patients. Dose escalation might overcome this resistance if detected early. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib provide effective therapeutic options for managing patients resistant or intolerant to imatinib. Recent studies have shown that dasatinib and nilotinib provide quicker and potentially better responses than standard-dose imatinib when used as a first-line treatment. The goal of therapy for patients with CML is the achievement of a complete cytogenetic response, and eventually a major molecular response, to prevent disease progression to accelerated or blast phase. Selecting the appropriate TKI depends on many factors, including disease phase, primary or secondary resistance to TKI, the agent's side effect profile and its relative effectiveness against BCR-ABL mutations, and the patient's tolerance to therapy. In October 2010, NCCN organized a task force consisting of a panel of experts from NCCN Member Institutions with expertise in the management of patients with CML to discuss these issues. This report provides recommendations regarding the selection of TKI therapy for the management of patients with CML based on the evaluation of available published clinical data and expert opinion among the task force members.
Pharmacotherapy for Chronic Myelogenous Leukemia: A Case-Based Approach
Authors: Harnicar Stephen
Published: April 2017

TKIs have become the standard of care for CML. Imatinib was the first to transform the outcomes of this disease. Dasatinib and nilotinib were recently added to the armamentarium for imatinib-resistant disease and, more recently, for first-line therapy. When choosing a TKI for patients, adverse effects, presence of mutations in the BCR-ABL kinase domain, and cost should be considered. Once chosen, drug interactions should be evaluated for all patients. New drugs are being studied to prevent disease progression and for patients with T315I mutations. This article reviews the pharmacotherapy of CML with the aid of a patient case.