bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating Rare Cancer in Children: The Importance of Evidence
Authors: Pappo Alberto S. 
Published: February 2020

Overview: The study of pediatric rare cancers, which account for approximately 9% of all childhood malignancies, has been hindered by their histologic heterogeneity and by their preferential occurrence in adolescents, a population that has been underrepresented in clinical trials sponsored by the National Cancer Institute. The use of cooperative group and investigator-initiated registries can help improve our ability to identify and select populations of patients with rare cancers that can benefit from single-arm studies, and incorporation of biologic aims and tissue banking can accelerate our understanding of the biology of these cancers. These studies should be promoted further through expansion of international outreach efforts. Well-designed preclinical models that accurately recapitulate human disease offer an attractive alternative to the study of rare cancers and may accelerate the process of target identification and drug discovery and development. The concept of specialized clinics for selected rare cancers has proven to be very successful in pediatric gastrointestinal tumors. This paradigm should be further explored in other rare cancers because it offers an unprecedented opportunity to collaborate closely with interested investigators. In addition, it offers patients an opportunity to discuss their disease with specialists, allows these patients to provide tissue for further research, and ultimately can promote the development of clinical trials that are unique for that specific disease.
Maintenance Therapy for Myeloma: How Much, How Long, and at What Cost?
Authors: Attal Michel , Roussel Murielle 
Published: February 2020

Overview: Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades and has been without evidence of clear advantage in terms of progression-free survival (PFS) until the mid-2000s. Neither conventional chemotherapy, prednisone, nor interferon-based maintenance regimens offered any benefit after conventional or high-dose therapy. Thalidomide was the first drug, mainly given as maintenance after high dose therapy, to demonstrate clinical benefits in terms of PFS and, in some studies, of overall survival (OS). The role of other novel agents such as lenalidomide and bortezomib as maintenance therapy is emerging. Lenalidomide has been shown to reduce the risk of relapse with longer follow-up needed to see if this will translate into a survival benefit. At present, a number of key questions remain unanswered. What are the optimal dose and duration of those treatments? Is the risk of toxicity and second primary malignancies acceptable? Will the disease be more aggressive at time of relapse? Is the clinical benefit predicted by initial prognostic factors and response to previous therapy? Does maintenance therapy work by further eradication of minimal residual disease or by immunological control of the malignant clone? Ongoing randomized trials are evaluating lenalidomide and bortezomib, both in the transplant and nontransplant settings, to better define the role of these drugs as maintenance in multiple myeloma.
Classification of Myeloproliferative Neoplasms and Prognostic Factors
Authors: Passamonti Francesco 
Published: February 2020

Overview: Myeloproliferative neoplasms (MPNs) are currently diagnosed according to the World Health Organization (WHO) criteria. Molecular profiling should include the analysis of JAK2 V617F (first, exon 12 only in V617F-negative polycythemia vera [PV]) and MPL mutations (in V617F-negative essential thrombocythemia [ET] and myelofibrosis [MF]). For patients with PV and ET, the risk stratification of low- and high-risk disease requires only two parameters: older than age 60 and prior history of thrombosis. Additionally, it might be important to monitor leukocyte count and know the mutational profile. Survival of patients with MF is defined by the International Prognostic Scoring System (IPSS) model at diagnosis and the Dynamic IPSS (DIPSS) anytime during the course of the disease. The IPSS and the DIPSS are based on patient age older than age 65, presence of constitutional symptoms, hemoglobin level less than 10 g/dL, leukocyte count greater than 25 × 109/L, and circulating blast cells 1% or greater. The DIPSS-plus adds critical prognostic information and suggests also considering cytogenetic categories, platelet count, and red blood cell transfusion need.
A Dickens Tale of the Treatment of Advanced Breast Cancer: The Past, the Present, and the Future
Authors: Sledge George W. , Cardoso Fatima , Winer Eric P. , Piccart Martine J. 
Published: February 2020

Overview: Metastatic breast cancer (MBC), a usually incurable disease, continues to vex physicians and patients. Recent decades have seen great improvements in the treatment of MBC, based on the availability of novel targeted therapeutics and more standard chemotherapeutic agents. This article describes the goals of therapy for MBC, the progress made against MBC in recent decades, the current standard of care, and the ongoing efforts of basic and translational researchers to transfer the fruits of modern scientific discovery to patients in the clinic.
Desmoid-Type Fibromatosis in Children: A Step Forward in the Cooperative Group Setting
Authors: Pounds Natalie , Skapek Stephen X. 
Published: February 2020

Overview: Desmoid-type (aggressive) fibromatosis (desmoid tumor) is a soft tissue neoplasm that can occur in both children and adults. Although it is formally classified as an intermediate-grade neoplasm because of its propensity for locally invasive growth, it can lead to severe and life-threatening problems. Because metastases do not arise from desmoid tumor, therapeutic interventions have historically focused on surgery or radiation to achieve local tumor control. These approaches may be ineffective or impractical for some children. In those cases, systemic therapy with cytotoxic or noncytotoxic therapy has been used. Because of the relative rarity of this neoplasm in children, knowledge on the use of chemotherapy is based largely on anecdotal reports or retrospective series. Limited conclusions can be drawn, though, from these types of reports. In the last 10 years, two prospective phase II clinical trials of chemotherapy for children with desmoid tumor have been conducted in cooperative clinical trials centered in North America. We review the results of those clinical trials and suggest future directions for systematically approaching this disease to better define the role of chemotherapy for children with desmoid tumor.
Surgical Treatment of Colorectal Cancer Liver Metastases
Authors: Curley Steven A. 
Published: February 2020

Overview: Treatment strategies for patients with stage IV colorectal cancer have changed markedly in the last decade. Patients with colorectal cancer metastases to the liver have always been a fascinating group to consider biologically and for local-regional treatment strategies. In the late 1980s through the 1990s, resection was performed for a select subset of patients who had resectable disease. However, a high proportion of patients had bilobar unresectable disease and were treated with either 5-fluorouracil–based systemic chemotherapy or implanted hepatic arterial infusion pumps. The advent of the new millennium was associated with the availability of several new cytotoxic and biologic agents active in colorectal cancer. These agents have completely changed the approach to the treatment of patients with colorectal cancer liver metastases and thus have increased the complexity of the decision-making process for treatment of these patients.
Management of Human Papillomavirus–Induced Oropharynx Cancer
Authors: Brizel David 
Published: February 2020

Overview: Oropharynx cancer (OPC) constitutes the most common location for squamous-cell head and neck cancer, and most OPC is caused by the human papilloma virus (HPV). Early-stage (American Joint Committee on Cancer [AJCC] stage I and II) disease should be treated with single modality surgery or radiotherapy whenever possible. More advanced presentations generally require combined-modality therapy with various combinations of surgery, radiotherapy, and chemotherapy or molecularly targeted therapy. All of these approaches expose patients to a substantial risk of serious long-term functional morbidity. HPV-induced OPC has a very favorable prognosis compared with its HPV-negative counterpart irrespective of the treatment platform that is used. Current clinical trials are investigating the concept of therapeutic deintensification with the dual objectives of decreasing toxicity and maintaining efficacy.
International Perspective on the Global Advances in Gynecologic Oncology
Authors: Denny Lynette 
Published: February 2020

Overview: The treatment of gynecologic cancer has evolved over the years, with greater emphasis on tailored surgery and reducing morbidity and mortality related to surgery, particularly in the management of vulvar and cervical cancer. The addition of concurrent chemotherapy to radiation regimens has improved survival of patients with cervical cancer in developed countries; however, most women with cancer in developing countries have advanced, untreatable disease and minimal access to anticancer therapies. In the past 15 years there has been intense research into alternatives to cervical cytologic testing, particularly in low resourced regions but also in an attempt to improve on cytologic testing in developed countries. Surgical staging in endometrial cancer has enabled the use of adjuvant radiation to be individualized to the patient's particular risk factors for recurrence. The management of ovarian cancer, long stagnant since the introduction of platinum and paclitaxel as chemotherapeutic agents, is set to change with the onset of molecular and genetic profiling and the introduction of novel therapies.
Dose-Dense Chemotherapy and Neoadjuvant Chemotherapy for Ovarian Cancer
Authors: Fujiwara Keiichi , Katsumata Noriyuki , Onda Takashi 
Published: February 2020

Overview: Two of the innovative chemotherapeutic approaches to ovarian cancer treatment, dose-dense chemotherapy and neoadjuvant chemotherapy, will be discussed herein. The primary concept of dose-dense chemotherapy is to administer the same cumulative dose of chemotherapy over a shorter period. Increased dose density is achieved by reducing the interval between each dose of chemotherapy. The Japanese Gynecologic Oncology Group (JGOG) first demonstrated the survival advantage of dose-dense weekly administration of paclitaxel in 2009. However, there are unanswered questions, such as the question of dose-dense carboplatin versus less dose-intensive regimens. Clear cell or mucinous carcinomas seem to need other strategies, such as targeted agents. The aim of neoadjuvant chemotherapy is to reduce tumor volume or spread before main treatment. This could then make the main procedures easier or less invasive, just like breast-conserving surgery after neoadjuvant chemotherapy. In advanced ovarian cancer, standard procedure is maximum primary debulking surgery followed by chemotherapy. Recently, a prospective randomized trial demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to the standard procedure. However, there are several questions that remain unanswered, such as the suitable number of chemotherapy cycles before interval debulking surgery. Some of those questions regarding dose-dense chemotherapy or neoadjuvant chemotherapy may be resolved by ongoing or future prospective trials.
Treatment of Chronic Myelogenous Leukemia as a Paradigm for Solid Tumors: How Targeted Agents in Newly Diagnosed Disease Transformed Outcomes
Authors: Westin Jason R. , Kantarjian Hagop , Kurzrock Razelle 
Published: February 2020

Overview: Although chronic myelogenous leukemia (CML) is rare, with approximately 5000 new cases in the United States annually, it may be the poster child for the future of oncology. Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor (TKI), transformed the course of CML from a rapidly fatal disease (median survival, 3 to 6 years) to a functionally curable, indolent disease with an estimated median survival of more than 25 years. This transformation can be attributed to several key factors: the identification of a causal and actionable molecular aberration— BCR-ABL; the development of a potent and selective Bcr-Abl TKI—imatinib; and, importantly the application of imatinib in the earliest phase of CML. In contrast, imatinib, if used in CML blastic phase, improves median survival to only about 1 year. Similar to CML blastic phase, metastatic solid malignancies have undergone genetic evolution, and their molecular aberrations are complex. As a result, resistance is common and eradication is difficult. The key to the dramatic improvement in the survival of patients with CML involved using imatinib in newly diagnosed disease, before blastic transformation. We hypothesize that metastatic solid tumors are analogous to CML blastic phase, and that to achieve improvements in solid tumor outcomes similar to those seen in CML, application of targeted agents to newly diagnosed disease may be required to prevent disease transformation (i.e., metastases). Targeting driver mutations at the time of diagnosis may be critical to the goal of markedly changing the outlook for patients with cancer.
How Does Biology Affect Local Therapy Decisions?
Authors: Buchholz Thomas A. 
Published: February 2020

Overview: Breast cancer represents a biologically diverse set of diseases. Previous data suggest that the estrogen/progesterone receptor (ER/PR) status and HER2/ neu status are important determinants of prognosis and response to various systemic treatments. Recent data also suggest that these receptors correlate with outcomes of local-regional therapies. Specifically, patients with ER-positive HER2/ neu-negative disease have an excellent outcome with radiation treatments, either given as a component of breast-conservative therapy (BCT) or for those with more advanced disease, when given after mastectomy. For patients with triple-negative disease, data suggest that the proportional benefits offered from radiation in reducing local-regional recurrences may be less. This article will highlight some of these data and discuss strategies for new local-regional research avenues that are based on breast cancer biologic subtype.
Intraperitoneal Treatment in Ovarian Cancer: The Gynecologic Oncology Group Perspective in 2012
Authors: Armstrong Deborah K. , Fujiwara Keiichi , Jelovac Danijela 
Published: February 2020

Overview: The peritoneal cavity is the major site of disease in ovarian cancer. The peritoneal predominance of disease provides a rationale for administration of chemotherapy within the peritoneal cavity. Intraperitoneal (IP) chemotherapy for ovarian cancer has been studied rigorously for more than 30 years and has been reproducibly shown to improve the survival of patients with ovarian cancer. Three large randomized trials of IP compared with intravenous (IV) therapy have demonstrated statistically significant improvement in clinical outcome measures. Despite this, the IP approach has not gained widespread acceptance in the treatment of ovarian cancer. Here, we review reported, recently completed, and ongoing trials of IP therapy in ovarian cancer including attempts to improve the tolerability and acceptance of this proven approach.
Capturing the Patient Perspective: Patient-Reported Outcomes as Clinical Trial Endpoints
Authors: Bruner Deborah Watkins , Movsas Benjamin , Basch Ethan 
Published: February 2020

Overview: Just as clinical trial design and rigor have evolved with improvements in methods and processes, so too have methods for capturing patient data in clinical trials. Substantial evidence suggests that standard physician reporting of symptoms for which we lack objective diagnostics (e.g., pain) is often discordant with patient self-report. Current reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTC[AE]) for symptom capture relies on a filtering system, from patient to physician to medical record to medical record abstraction to data entry, with each step requiring interpretation and the possibility of error. In contrast, patient-reported outcomes (PROs) eliminate the filter and rely on direct report. Furthermore, the lack of validation and training in use of the CTC(AE) creates an inadequate data capture system. Inadequacies might be observed as underreporting or overreporting symptom prevalence and severity compared with patient self-report. Inaccuracies in symptom reporting can lead to missing important prognostic information, lack of understanding of patient adherence with therapies, and lack of information for patient decision making. They can also lead to opportunities lost in terms of labeling claims and comparative effectiveness analyses. New developments in patient-reported outcome (PRO) reporting, including the PRO-CTC(AE) and models for incorporation of PROs in clinical trials, might facilitate routine PRO reporting complementary to CTC(AE) in clinical trials. In addition, the cadre of validated PRO instruments already in existence allows for more in-depth, hypothesis-driven evaluations. For standard toxicity reporting, the time has come for mandatory routine PRO symptom reporting complementary to the CTC(AE).
A Balanced Approach to Physician Responsibilities: Oncologists' Duties toward Themselves
Authors: Abernethy Amy P. 
Published: February 2020

Overview: Although critical to the provision of best patient care, physician self-care is an underattended aspect of responsibility in the medical professions, including oncology. Neglecting self-care bears negative consequences for the individual oncologist, ranging from burnout and fatigue to interpersonal and relationship stress, addiction, and disruptive behavior. It may also contribute to medical errors, disinterest in or depersonalization of patient care, and lower quality of care. Because of its effect on physicians, patients, and the health care environment, physician self-care is increasingly recognized as an important professional responsibility. Nonetheless, professional obligations, competing demands on time, and personal priorities conspire to prevent a large proportion of oncologists from adequately attending to self-care in even simple ways, such as getting sufficient exercise and sleep. This chapter discusses the need for physician self-care and the repercussions of not meeting this fundamental responsibility. Self-care is described in the context of three life domains: professional, personal (physical, psychological, mental, and spiritual), and interpersonal (relationships, family, social, and community). Strategies are provided for caring for the self in each domain.
New Developments in Prostate Cancer Therapy
Authors: Bajaj Madhuri , Heath Elisabeth I. 
Published: February 2020

Overview: Prostate cancer is the most common nonskin malignant neoplasm in men worldwide. In the United States, 241,740 new diagnoses of prostate cancer and 28,170 prostate cancer deaths have been estimated for 2012, representing 28% of new cancer cases and 10% of male cancer deaths. 1 Although metastatic prostate cancer remains an incurable disease, substantial advances have been made in therapeutic options available for men in the past several years. Development of novel agents that modulate the androgen receptor pathway, growth factor signaling pathways, and immune function and bone targeting pathways has been the focus of therapeutic strategies because of its significance in the biology of prostate cancer progression. Several of the agents have gained U.S. Food and Drug Administration (FDA) approval, whereas many are in late-stage clinical trials. With the growth of available treatment options, a major challenge as we move forward will be to determine the best sequence and/or combination of therapy that will result in maximum clinical efficacy with minimum toxicity. Highlighted in this publication are several of the exciting advances in prostate cancer therapy for patients with metastatic, castrate-resistant prostate cancer.
Genetic Alterations in Childhood Melanoma
Authors: Navid Fariba 
Published: February 2020

Overview: Melanoma is rare in children. However, the clinical features of the disease in this population have been well-documented through single-institution experiences and population-based analyses. Still, our understanding of the etiologic factors in children remains unclear and diagnosis of melanoma remains challenging in certain cases. This article reviews emerging evidence indicating that molecular characterization of these lesions in children may be of diagnostic and therapeutic value.
Kinetic models of the extraction of vanillic acid from pumpkin seeds
Authors: Mitić Milan , Janković Sonja , Mašković Pavle , Arsić Biljana , Mitić Jelena , Ickovski Jovana 
Published: February 2020

AbstractVanillic acid is used in the food industry and perfumery, and the optimization of its extraction process from the natural source is important for saving time and money. The presence of vanillic acid in pumpkin seeds was proven using HPLC analysis. Computational optimization of the extraction shows that for the concentration of ethanol 40% and solmodul: V/m=20, the optimum condition for the extraction of vanillic acid from pumpkin seeds was 100 min and 450C. The estimation of fitting for each kinetic model to the experimental kinetic data was performed using the root mean square, standard deviation, and the correlation coefficient. Ponomarev model was shown as the most suitable with the highest accuracy among the six considered kinetic models. The enthalpy and entropy changes were positive, while the Gibbs free energy was negative and decreased when temperature increased during the thermodynamic analysis. Therefore, the extraction of vanillic acid from pumpkin seeds was endothermic, spontaneous, and irreversible.
Block-Adaptive Cross Approximation of Discrete Integral Operators
Authors: Bauer Maximilian , Bebendorf Mario 
Published: February 2020

Abstract
In this article, we extend the adaptive cross approximation (ACA) method known for the efficient approximation of discretisations of integral operators to a block-adaptive version.
While ACA is usually employed to assemble hierarchical matrix approximations having the same prescribed accuracy on all blocks of the partition, for the solution of linear systems, it may be more efficient to adapt the accuracy of each block to the actual error of the solution as some blocks may be more important for the solution error than others.
To this end, error estimation techniques known from adaptive mesh refinement are applied to automatically improve the blockwise matrix approximation.
This allows to interlace the assembling of the coefficient matrix with the iterative solution.