bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical Sphincter Preservation in Rectal Cancer
Authors: Schlag P.M. 
Published: February 2020

Abstract
Improved understanding of the biological features and advances in diagnostic and surgical procedures have been the basis for increased applications of sphincter preserving operations in lower rectal tumors. The relevant treatment strategies along with their indications will be presented and analyzed. New operative procedures comprise transanal excision of early rectal cancer or trans-sphincteric resection or ultralow anterior resection with colon-pouch creation to improve continence. Recently, for cases in which the removal of the rectal sphincter is indispensable for oncological reasons, a continent perineal colostomy has been developed. Reconstruction of the sphinter function is achieved using a seromuscular cuff. This procedure avoids an abdominal colostomy. The neosphincter can also be formed secondarily, after a prior abdomino-perineal excison with transabdominal colostomy.
Congenital Marrow Failure Syndromes and Malignant Hematopoietic Transformation
Authors: Freedman Melvin H. 
Published: February 2020

Abstract
In the current era of advanced supportive care and administration of recombinant cytokines and other effective therapies, patients with congenital (inherited) marrow failure syndromes usually survive the early years of life and beyond. With the extended lifespan, a new “natural history” for these syndromes is evident. Although these disorders were always classified as “benign” historically, it is now evident that most of these conditions confer an inordinately high predisposition to myelodysplastic syndromes and acute myelogenous leukemia (MDS/AML). Since carcinogenesis occurs as a sequence of events that is driven by genetic damage and by epigenetic changes, the hypothesis is advanced that the first “hit” or leukemia-initiating step is the constitutional genetic mutation, itself, that initially manifests as a single lineage or multiple lineage marrow failure. The leukemic promotion and progression steps leading to MDS/AML can then ensue readily in the initiated pool of progenitors or stem cells. Thus, the distinction between benign and malignant hematology in the context of the inherited marrow failure disorders has become blurred and new definitions for these syndromes should be developed.
Aplastic Anemia, Pediatric Aspects
Authors: Alter Blanche P. 
Published: February 2020

Abstract
Inherited bone marrow failure syndromes (BMFs) comprise at least one-fourth of children with aplastic anemia, and perhaps up to 10% of adults. The most common syndrome is Fanconi's anemia (FA), with more than 1,000 reported cases. FA is autosomal recessive, with birth defects in ~75% of patients. It is a DNA repair syndrome, diagnosed by finding chromosomal aberrations in cells treated with clastogenic agents. The major problems in FA are, in order, aplastic anemia, leukemia, and other cancers. There are at least five complementation groups; the gene for Group C has been cloned. Carrier identification and gene therapy are beginning in families at risk for FAC mutations. Dyskeratosis congenita (DC) is primarily X-linked (at Xq28), with autosomal recessive and dominant cases as well. Patients classically have reticulated hyperpigmented skin, dystrophic nails, and mucous membrane leukoplakia. ~50% develop aplastic anemia, sometimes prior to the DC phenotype, and ~10% develop cancer. Shwachman-Diamond syndrome consists of exocrine pancreatic insufficiency with neutropenia; ~25% develop aplastic anemia and 5%-10% develop leukemia. Amegakaryocytic thrombocytopenia presents in infancy, and often evolves into aplastic anemia and/or leukemia. Single cytopenias include Diamond-Blackfan anemia (DBA), which is inherited pure red cell aplasia; transient erythroblastopenia of childhood; Kostmann's syndrome (KS) or infantile genetic agranulocytosis, and thrombocytopenia with absent radii in which there is neonatal thrombocytopenia and absent radii. DBA and KS, particularly the latter treated with G-CSF, may develop leukemia, and solid tumors have been reported in DBA. Treatment for the various BMFs includes bone marrow transplantation, androgens, and hematopoietic cytokines such as G-CSF. These inherited syndromes thus include various combinations of marrow failure and premalignancy.
The Value of Laparoscopic Staging in Upper Gastrointestinal Malignancy
Authors: Conlon Kevin C. P. , Minnard Emery A. 
Published: February 2020

Abstract
The goal of the clinical staging of malignant disease is to accurately define the extent of disease, direct appropriate therapy and avoid unnecessary intervention. Recent reports have suggested that laparoscopy can play a useful and complementary role in the staging of abdominal malignancy. This paper reviews the recent experience with laparoscopy in the staging of patients with upper gastrointestinal malignancy.
Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer
Authors: McLeod David G. 
Published: February 2020

Abstract
This review compares the tolerability profiles of the three currently available nonsteroidal antiandrogens, flutamide, bicalutamide and nilutamide. Pharmacological effects associated with blockade of the androgen receptor are frequent with all three drugs. Gynecomastia and breast pain are seen more frequently during antiandrogen monotherapy than during combination with medical or surgical castration or castration alone, and the reverse is true for hot flashes, which are a side effect of castration. Gastrointestinal symptoms are also common to all three drugs, but diarrhea occurs more frequently in flutamide studies than in bicalutamide or nilutamide studies. Hepatotoxicity has been seen with all three antiandrogens, but acute, reversible hepatitis and fatal fulminant hepatitis have also been reported with both nilutamide and flutamide. All three drugs have been associated with asymptomatic elevations in aminotransferases and may reduce hemoglobin levels. Adverse events that have been reported with nilutamide include interstitial pneumonitis, delayed adaptation to darkness after exposure to bright light and alcohol intolerance. To date, bicalutamide appears to have some advantage over flutamide and nilutamide in terms of tolerability.
Adjuvant Chemotherapy in Advanced Head and Neck Cancer
Authors: Amrein Philip C. , Colecchi Christopher H. , Finkelstein Dianne M. , Fabian Richard L. 
Published: February 2020

Abstract
Purpose. Chemotherapy has been tested extensively in conjunction with standard therapy in the treatment of head and neck cancer, primarily in the form of neoadjuvant chemotherapy, but few trials have shown a survival benefit. Although a few studies have suggested that adjuvant chemotherapy given after standard treatment may improve survival, to date these trials have been troubled by various problems in design and dosing. The purpose of our trial was to determine the feasibility of giving moderately intensive chemotherapy exclusively after standard therapy, and to determine whether survival appeared to be improved as measured against historical data.
Methods. We used adjuvant chemotherapy in two groups of patients with squamous cell carcinoma of the head and neck: group A consisted of 46 patients with newly diagnosed stage III and IV disease, and group B consisted of 46 patients with relapsed disease having been treated with salvage surgery. In all patients, the intended adjuvant chemotherapy consisted of two cycles of combination cisplatin, bleomycin, and infusional 5-fluorouracil (5-FU) given three weeks apart, followed by four cycles of bolus methotrexate, 5-FU, and bleomycin given every two weeks.
Results. In group A, the two-year survival was 72%. In group B, the two-year survival was 58%.
Conclusion. Compared to the vast majority of similarly staged patients with head and neck cancer reported in the literature, the survival of our group seemed considerably better, suggesting that a definitive randomized study testing this schedule of adjuvant chemotherapy is warranted.
Moving Forward with Capecitabine: a Glimpse of the Future
Authors: Biganzoli Laura , Martin Miguel , Twelves Chris 
Published: February 2020

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Appreciate the emerging role of capecitabine monotherapy in the treatment of advanced breast cancer. Explain the current status of capecitabine monotherapy as first or second line therapy in patients with advanced breast cancer. Describe the rationale and current status of capecitabine combination treatment of breast cancer. Balance the safety profile of capecitabine with available alternative treatment options for the treatment of advanced breast cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Oral capecitabine is a useful chemotherapy for metastatic breast cancer, both as monotherapy and in combination with other cytotoxic drugs. The proven activity of capecitabine has provided the rationale to explore its use earlier in the course of the disease and in combination with other agents, particularly those known to further upregulate thymidine phosphorylase (TP) concentrations in tumor tissue.
The efficacy and safety of capecitabine monotherapy compares favorably with cyclophosphamide/methotrexate/5-fluorouracil in chemotherapy-naïve patients and with paclitaxel in anthracycline-pretreated patients. Therefore, for patients whose disease has progressed during or following anthracycline treatment, but for whom capecitabine/docetaxel combination therapy or taxane monotherapy is not appropriate, capecitabine monotherapy is an attractive alternative to established i.v. treatments.
In combination, capecitabine plus paclitaxel, which further upregulates TP in tumor tissue, has demonstrated high activity in two phase II studies in advanced/metastatic breast cancer. Similarly, combination with vinorelbine showed promising activity in pretreated metastatic breast cancer patients, and triple combinations with an anthracycline and a taxane or cyclophosphamide have proven to be highly active. In the future, capecitabine may be combined with novel biologic agents, such as trastuzumab and bevacizumab; the former combination has already shown encouraging results in a pilot trial. Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted.
Understanding the Financial Needs Following Diagnosis of Breast Cancer in a Setting with Universal Health Coverage
Authors: Kong Yek-Ching , Wong Li-Ping , Ng Chiu-Wan , Taib Nur Aishah , Bhoo-Pathy Nanthini Thevi , Yusof Mastura Mohd , Aziz Azlina Firzah , Yehgambaram Prathepamalar , Ishak Wan Zamaniah Wan , Yip Cheng-Har , Bhoo-Pathy Nirmala 
Published: February 2020

Abstract

Background
A diagnosis of cancer negatively impacts the financial wellbeing of affected individuals as well as their households. We aimed to gain an in-depth understanding of the financial needs following diagnosis of breast cancer in a middle-income setting with universal health coverage.

Materials and Methods
Twelve focus group discussions (n = 64) were conducted with women with breast cancer from two public and three private hospitals. This study specifically focused on (a) health costs, (b) nonhealth costs, (c) employment and earnings, and (d) financial assistance. Thematic analysis was used.

Results
Financial needs related to cancer treatment and health care varied according to the participant's socioeconomic background and type of medical insurance. Although having medical insurance alleviated cancer treatment-related financial difficulties, limited policy coverage for cancer care and suboptimal reimbursement policies were common complaints. Nonhealth expenditures were also cited as an important source of financial distress; patients from low-income households reported transport and parking costs as troublesome, with some struggling to afford basic necessities, whereas participants from higher-income households mentioned hired help, special food and/or supplements and appliances as expensive needs following cancer. Needy patients had a hard time navigating through the complex system to obtain financial support. Irrespective of socioeconomic status, reductions in household income due to loss of employment and/or earnings were a major source of economic hardship.

Conclusion
There are many unmet financial needs following a diagnosis of (breast) cancer even in settings with universal health coverage. Health care professionals may only be able to fulfill these unmet needs through multisectoral collaborations, catalyzed by strong political will.

Implications for Practice
As unmet financial needs exist among patients with cancer across all socioeconomic groups, including for patients with medical insurance, financial navigation should be prioritized as an important component of cancer survivorship services, including in the low- and middle-income settings. Apart from assisting survivors to understand the costs of cancer care, navigate the complex system to obtain financial assistance, or file health insurance claims, any planned patient navigation program should also provide support to deal with employment-related challenges and navigate return to work. It is also echoed that costs for essential personal items (e.g., breast prostheses) should be covered by health insurance or subsidized by the government.
Treatment Patterns and Health Resource Use Among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Treated at a Tertiary Referral Center
Authors: Jalbert Jessica J. , Casciano Roman , Meng Jie , Brais Lauren K. , Pulgar Sonia J. , Berthon Anthony , Dinet Jerome , Kulke Matthew H. 
Published: February 2020

Abstract

Background
Although an increasing number of treatments have become available for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), there remains little consensus on treatment sequence and its impact on health care resource use (HRU). We sought to describe treatment patterns and HRU, in a cohort of patients with metastatic GEP-NETs treated at a tertiary referral center in the U.S.

Materials and Methods
We identified patients with a well-differentiated, metastatic GEP-NET evaluated at Dana-Farber Cancer Institute between July 2003 and May 2015. For these patients, we describe the sequence of treatment regimens received for their disease, together with associated HRU.

Results
We identified 682 patients with advanced GEP-NETs. Of these patients, 597 (87.0%) initiated ≥1 treatment over the follow-up period. The mean age at diagnosis was 58.5 years, 50.2% were men, and 94.0% were white. A total of 83.1% initiated a somatostatin analog (SSA) as their first-line treatment, with 55% and 31% of patients continuing with second- and third-line therapies. A total of 31.2% of patients with SSAs underwent dose escalation to above standard dose. In this setting, patients with pancreatic neuroendocrine tumors were more commonly treated with cytotoxic regimens than other NET tumor types and also had higher HRU.

Conclusion
Our study suggests that, at a tertiary referral center, patients with advanced NETs commonly received multiple courses of treatments. Our data suggest a clear preference for use of SSAs as a first-line treatment for patients with advanced NETs, with SSAs commonly escalated and continued throughout the course of treatment in combination with other regimens.
Phase I Trial of a Modified Vaccinia Ankara Priming Vaccine Followed by a Fowlpox Virus Boosting Vaccine Modified to Express Brachyury and Costimulatory Molecules in Advanced Solid Tumors
Authors: Collins Julie M. , Donahue Renee N. , Tsai Yo-Ting , Manu Michell , Palena Claudia , Gatti-Mays Margaret E. , Marté Jennifer L. , Madan Ravi A. , Karzai Fatima , Heery Christopher R. , Strauss Julius , Abdul-Sater Houssein , Cordes Lisa , Schlom Jeffrey , Gulley James L. , Bilusic Marijo 
Published: February 2020

Abstract

Lessons Learned
Modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury followed by fowlpox virus-BN-Brachyury was well tolerated upon administration to patients with advanced cancer. Sixty-three percent of patients developed CD4+ and/or CD8+ T-cell responses to brachyury after vaccination. BN-Brachyury vaccine also induced T-cell responses against CEA and MUC1, which are cascade antigens, that is, antigens not encoded in the vaccines.

Background
Brachyury, a transcription factor, plays an integral role in the epithelial–mesenchymal transition, metastasis, and tumor resistance to chemotherapy. It is expressed in many tumor types, and rarely in normal tissues, making it an ideal immunologic target. Bavarian Nordic (BN)-Brachyury consists of vaccination with modified vaccinia Ankara (MVA) priming followed by fowlpox virus (FPV) boosting, each encoding transgenes for brachyury and costimulatory molecules.

Methods
Patients with metastatic solid tumors were treated with two monthly doses of MVA-brachyury s.c., 8 × 108 infectious units (IU), followed by FPV-brachyury s.c., 1 × 109 IU, for six monthly doses and then every 3 months for up to 2 years. The primary objective was to determine safety and tolerability.

Results
Eleven patients were enrolled from March 2018 to July 2018 (one patient was nonevaluable). No dose-limiting toxicities were observed. The most common treatment-related adverse event was grade 1/2 injection-site reaction observed in all patients. Best overall response was stable disease in six patients, and the 6-month progression-free survival rate was 50%. T cells against brachyury and cascade antigens CEA and MUC1 were detected in the majority of patients.

Conclusion
BN-Brachyury vaccine is well tolerated and induces immune responses to brachyury and cascade antigens and demonstrates some evidence of clinical benefit.
Cancer-Related Fatigue: Guidelines for Evaluation and Management
Authors: Portenoy Russell K. , Itri Loretta M. 
Published: February 2020

Abstract
Fatigue is a highly prevalent condition among cancer patients. Although most cancer patients report that fatigue is a major obstacle to maintaining normal daily activities and quality of life, it is seldom assessed and treated in clinical practice. Few studies have explored its epidemiology, possible etiologies, or management. Cancer-related fatigue, which recently was accepted as a diagnosis in the International Classification of Diseases 10th Revision-Clinical Modification, reduces physical, psychological, and social functioning and results in significant distress for patients and caregivers. Adequate evaluation of fatigue must do more than simply assess severity. The assessment should clarify other characteristics, determine the degree to which fatigue interferes with the activities of daily living, and identify potential causes, including the underlying disease, disease treatments, intercurrent systemic disorders, psychological disorders, and other conditions. Possible primary therapies include modification of the patient's drug regimen, correction of metabolic abnormalities, and pharmacologic treatments for anemia (e.g., epoetin alfa), depression, or insomnia. Other symptomatic interventions include specific drug treatments, exercise, modification of activity and rest patterns, cognitive therapies, sleep hygiene approaches, and nutritional support. Pharmacologic approaches, which are supported by limited studies and growing clinical experience, include psychostimulant drugs, corticosteroids, and possibly other therapies. Although additional research is needed to further identify the causes and corresponding treatment of fatigue, practitioners should routinely assess and treat patients who may benefit from currently identified interventions, because fatigue can profoundly undermine the quality of life of patients with cancer.
Long-Term Survivors of Childhood Cancer: The Late Effects of Therapy
Authors: Schwartz Cindy L. 
Published: February 2020

Abstract
The successful treatment of pediatric malignancy by multimodality therapy has improved the outcome for children with cancer. It has been estimated that 0.1% of individuals 20 years of age are survivors of childhood cancer. This represents a large cohort nationally who, with maturation, may be increasingly beset by the medical and social consequences of treatment.
The study of long-term effects of cancer chemotherapy has grown enormously in the past decade. Any side effect that does not resolve after the completion of therapy is a long-term effect of therapy. Side effects recognized during the therapeutic period are usually addressed by the treating physicians. More problematic are those effects of therapy that are subclinical at completion of therapy but manifest years later. These are the true late effects of therapy and are the focus of this review.
The cytotoxic effects on maturing tissues become apparent only with development. Thus physical, intellectual and pubertal development as well as reproductive potential may be impossible to assess for a decade or more, depending upon the age at the time of treatment. Nonetheless, the ability to predict the likelihood of a given adverse outcome is enormously helpful to the survivor and may allow for the mitigation of severe effects.
Organ injury may also be subclinical initially. With aging and additional stress, compensatory mechanisms may fail. The development of effective screening methodologies may be essential for early interventions. Lifestyle changes may reduce exposure to further toxins and mutagenic agents such as alcohol and cigarette smoke that may lead to secondary malignancy, particularly if compounded in some instances by genetic predisposition.
Programs for survivors of childhood cancer were developed within pediatric oncology. As the children become adults, the likelihood of continued care at the initial treating institution decreases. Oncologists and other health care professionals who become responsible for the health care of this maturing cohort will need to understand the risks engendered by childhood cancer therapy.
A Staff Dialogue on Do Not Resuscitate Orders: Psychosocial Issues Faced by Patients, Their Families, and Caregivers
Authors: O'Shea Elizabeth M. , Penson Richard T. , Stern Theodore A. , Younger Jerry , Chabner Bruce A. , Lynch Thomas J. 
Published: February 2020

AbstractShortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.The following case of a woman who developed lymphoma was discussed at the July and August, 1997 Schwartz Center Rounds. There were considerable delays and uncertainties in the diagnosis, which was followed by an unpredictably chaotic clinical course. Although she had made it clear to her doctor that she did not want “heroic measures,” she had unexpectedly rallied so many times that her son and her husband wanted her doctors to do everything possible to keep her alive, including the performance of cardiopulmonary resuscitation (CPR). The clinical benefit of CPR in the event of cardiac arrest in those with cancer is discussed, as are do not resuscitate (DNR) orders, living wills, and healthcare proxies. In addition, the issues that surround DNR status, including who should discuss DNR status with a patient, and how and when it should be discussed, are reviewed. Staff raised concerns about the effect of discussing DNR status on the doctor-patient relationship, and wondered whether writing DNR orders adversely affect the care of patients.