bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Human Erythropoietin (rHuEPO) for the Treatment of the Anemia of Cancer
Authors: Abels R. I. , Larholt Kay M. , Krantz Kenneth D. , Bryant Edward C. 
Published: February 2020

Abstract
Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents. In a series of double-blind, placebo-controlled trials, three populations of anemic cancer patients were randomized to rHuEPO or placebo. The three populations were: A) patients not receiving concomitant chemotherapy, B) patients receiving chemotherapeutic regimens which did not contain cisplatin, and C) patients receiving chemotherapeutic regimens which contained cisplatin. In the no-chemotherapy trials, patients were treated with rHuEPO (100 U/kg) or placebo s.c. three times a week for up to eight weeks. In the two types of chemotherapy trials, patients were treated with rHuEPO (150 U/kg) or placebo SC three times a week for 12 weeks.
A total of 413 patients were enrolled in these trials (124 in the no-chemotherapy group, 157 in the no-cisplatin chemotherapy group and 132 in the cisplatin chemotherapy group). In each trial, patients randomized to rHuEPO had a significantly greater (p &lt; .004) increase in hematocrit than placebo-treated patients. In the two types of chemotherapy trials combined, utilizing an rHuEPO dose of 150 U/kg, rHuEPO-treated patients had significantly lower (p ≤ .009) transfusion requirements (percentage of patients transfused and mean units of blood transfused per patient) than placebo-treated patients during months two and three, but not during month one. Quality-of-life parameters measured on a 100 mm visual analog scale significantly improved (p&lt;.05) in rHuEPO-treated patients whose hematocrit increased ≥6 percentage points, compared to corresponding quality-of-life changes in placebo-treated patients. rHuEPO was well tolerated compared to placebo.
The above results suggest that rHuEPO may be a useful agent to palliate the morbid consequences of the anemia that is often found in association with advanced cancer.
In response to: Professor Cassileth's manuscript on “Alternative and Complementary Cancer Treatments,” featured in The Oncologist 1996;1:173-179.
Authors: Quah Thuan-Chong 
Published: February 2020

Abstract
Alternative and complementary therapies differ importantly, and the distinction between the two is crucial for clinical oncologists. “Alternative” or unproven therapies are treatments used independent of surgery, radiation and chemotherapy. They can be dangerous directly and also by delaying patients' receipt of mainstream care. In contrast, complementary therapies typically are adjuncts to mainstream medicine. They can provide symptom control and noninvasive palliation with minimal side effects, improve patients' well-being and enhance cancer medicine. Complementary therapies represent a desired addition and balance to technologically sophisticated cancer care.
Optimal Surgical Treatment of Breast Cancer
Authors: Veronesi Umberto , Zurrida Stefano 
Published: February 2020

Abstract
Large-scale, controlled trials in the 1970s and 1980s demonstrated that wide resection (for example, quadrantectomy) was as effective as mastectomy for the treatment of breast cancer up to 3 cm in maximum diameter. Conservative treatment may also be extended to larger cancers following pre-operative chemotherapy to reduce tumor mass and leave sufficiently wide resection margins to ensure oncological radicality. Quadrantectomy is an operation of curative intent, distinct from “lumpectomy” or “tumorectomy,” whose main aim is to debulk the tumor mass; nevertheless, wide resection should, in most cases, be flanked by radiotherapy to sterilize the tumor bed and by complete axillary dissection to remove any metastatic nodes and provide full prognostic information. This triple approach provides a high cure rate and low relapse rate for breast cancer, while providing an acceptable cosmetic outcome; we believe it is the optimal treatment for breast cancer at the present time. Modifications include simultaneous remodeling of the affected breast if, because of tumor position, the result of conservative surgery is less than satisfactory; and use of radioguided surgery to detect the sentinel node which, if not involved, may indicate that full axillary dissection is unnecessary.
The Myelodysplastic Syndromes
Authors: Cheson Bruce D. 
Published: February 2020

AbstractThe myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The MDS range from those with a relatively indolent course (e.g., refractory anemia with or without ringed sideroblasts) to more aggressive disorders (e.g., refractory anemia with excess blasts [RAEB], and RAEB in transformation [RAEB-T]), which may exhibit a clinical course indistinguishable from acute myeloid leukemia (AML). Supportive care is the standard treatment for most patients, particularly those who are elderly, with the judicious use of blood components and antibiotics. For younger patients with RAEB and RAEB-T, antileukemic therapy might be considered, since the outcome is similar to that of patients with AML. Promising new chemotherapy agents currently in clinical trials include the topoisomerase I inhibitor, topotecan. The only curative treatment for MDS is allogeneic bone marrow transplantation, with long-term survival in approximately 40%, but with treatment-related deaths in 25%-40%. Factors predicting outcome include age, cytogenetics, number of blasts, and others. Myeloid growth factors (e.g., G-CSF, GM-CSF), increase the granulocyte count in most patients and may be useful in the setting of an active infection, although the prophylactic use of these agents does not improve survival. Erythropoietin increases the hematocrit in about 20% of patients. Growth factors being evaluated for their role in enhancing platelet counts include interleukin 11, stem cell factor, and megakaryocyte growth and development factor (thrombopoietin). Newer strategies to improve the outcome of patients with MDS should be based on an increased understanding of the biology of these disorders.
Long-Term Spinal Opioid Therapy in Terminally Ill Cancer Pain Patients
Authors: Wagemans Michel F.M. , Zuurmond Wouter W.A. , Lange Jaap J. 
Published: February 2020

Abstract
In terminally ill cancer patients with refractory pain, long-term spinal opioid therapy may provide a profound analgesia with minimal side effects. The reversibility of the technique and its efficacy throughout the body and for different types of pain are important advantages. For epidural administration, it is preferable to use lipid soluble opioids (sufentanil). For intrathecal administration, morphine is the best choice. The advantages of intrathecal administration over epidural administration are the need for lower doses because of a more direct administration at the receptor site, the easy positioning of the catheter, and less risk for migration of the catheter. In severe refractory pain which does not respond to spinal opioids, the use of non-opioids (e.g., a local anesthetic or an alpha-2 adrenoreceptor agonist) as coanalgesics may be recommended for improving pain relief. Long-term spinal opioid therapy at home has been made possible by technical and organizational development. In home care, only one physician should be the manager for the patient. Coordination should be optimized among patient, family, general practitioner, oncologist, anesthesiologist, home nurse, technician, and pharmacist.
Classification of Non-Hodgkin's Lymphoma: A Proposal
Authors: Hernández José , Krueger Jo Ellen Cottey , Glatstein Eli 
Published: February 2020

Abstract
The pathology community has traditionally classified the non-Hodgkin's lymphomas (NHL) according to their histogenetic characteristics, an approach that has fostered the proliferation of multiple, often conflicting, lymphoma classification schemes with limited clinical relevance. The scientific acceptance of these histogenetically pure schemes is based on an implicit belief that all that is scientifically sound must adhere to linear dynamic theory; that is, that the elemental components of a system in a linear and direct fashion control the behavior of the whole. Non-linear dynamic theory, however, which has recently acquired acceptance within the scientific community, offers another equally valid approach to the classification of the NHL by acknowledging the inherent indeterminacy of nature. In other words, rather than classifying the NHL according to their cell of origin in the hopes that the elemental unit will predict the clinical outcome, we propose that pathologists accept the premise that nature is inherently unpredictable and define the NHL according to their clinical characteristics, such as natural history and response to therapy. Using these criteria, a proposed classification is discussed containing two major subtypes of lymphomas (indolent and aggressive) which can be further subdivided into five groups: the low-grade, or indolent, group includes the small lymphocytic and the follicular cleaved cell (small, and small, mixed) categories, while the high-grade, or aggressive, group includes the large-cell, the Burkitt's lymphoma, and the lymphoblastic lymphomas. Each of these groups is discussed in detail, with comparisons to the Revised European American Lymphoma classification to demonstrate clinical relevance. Although it is clear to us that the proposed scheme presented in this manuscript is not the only clinically valid one that can be constructed, it is equally clear that any scheme that is developed—in order to be considered valid—must be guided principally by its clinical relevance.
Vaccine Trials for the Clinician: Prospects for Tumor Antigens
Authors: Osanto Susanne 
Published: February 2020

AbstractRecent insights in antigen presentation, the identification of human tumor antigens, and the demonstration of MHC class-I-restricted cytotoxic T lymphocyte (CTL) recognition of peptides encoded by tumor antigen have renewed the interest and enthusiasm for the development of cancer vaccines. Melanoma serves as a paradigm of an immunogenic human tumor, and several tumor antigens, including MAGE, MART-1/Melan-A and gp100, recognized by CTLs, have now been isolated. Candidate antigens for novel vaccine trials may include HLA class-I-binding tumor peptides that serve as CTL epitopes, whole tumor protein, or DNA-based vaccines. Requirements for the use of peptides are that the patient's tumor presents the relevant CTL epitopes as used in the vaccine and expresses the appropriate MHC class-I-restricting molecule. Immunological monitoring may be facilitated when using peptide-based vaccines. Because optimal presentation of tumor antigens may depend on provision of appropriate costimulatory signals, it may be more advantageous to administer professional antigen-presenting cells (APCs), such as dendritic cells (DCs) pulsed with tumor peptide or protein, to cancer patients.Developments in molecular genetics have led to a new approach in vaccines consisting of cancer cells genetically engineered to express immunomodulatory molecules. This may result in increased antitumor responses to both gene-modified as well as unmodified tumor cells.The therapeutic approach is extended to vaccination trials with recombinant viruses containing the genes encoding tumor antigens, minigenes containing multiple CTL epitopes, or double recombinant vectors engineered to express both the tumor antigen and immunostimulatory molecules.Clinical peptide, protein, and DNA-based vaccine trials have recently been initiated. Thus far, exciting clinical remissions were obtained in melanoma patients following vaccination with HLA-A1-binding MAGE-3 peptide and in B-cell lymphoma patients immunized with autologous DCs pulsed with anti-idiotype protein, i.e., the individual patient's unique tumor antigen. Also, following injection of foreign HLA-B7 DNA into cutaneous melanoma metastases, T-cell migration into treated lesions and enhanced cellular immunity at the site of the tumor were shown in some patients. These encouraging results suggest that effective new vaccines in cancer will be identified.
Understanding the Myelodysplastic Syndromes
Authors: Kouides Peter A. , Bennett John M. 
Published: February 2020

AbstractThe myelodysplastic syndrome (MDS) remains challenging to the clinician in terms of diagnosis and management. The diagnosis is essentially one of exclusion in first ruling out other disorders that can also cause peripheral blood/bone marrow cell dysplasia and cytopenias. The distinguishing biological characteristic of MDS is that it is a clonal disorder of the marrow with impaired differentiation. Recent studies implicate extensive apoptosis as the explanation of the paradoxical observation of marrow hyperplasia but peripheral blood cytopenia. Neutropenia and/or neutrophil dysfunction account for the primary clinical manifestation of MDS in terms of an increased risk for infection, which is the leading cause of death in MDS. The clonal nature of MDS places it also at continual risk for transformation to acute leukemia. Predicting overall survival as well as the risk of AML transformation has been improved by the recent development of a scoring system (International Prognostic Scoring System) that incorporates three laboratory variables: percent of marrow blasts, degree of cytopenias, and presence of chromosomal abnormalities. Based on these variables, four prognostic subgroups can be delineated ranging from low risk with a median survival of 5.7 years, to high risk with a median survival of 0.4 years. Management of MDS can now be based on the patient's respective prognostic subgrouping, with low-risk patients being considered for hematopoietic growth factor singly or in combination if at the point of red cell transfusion dependence and/or neutropenia with recurrent infections, while high-risk patients should be offered AML-induction therapy or novel agents such as Topotecan. One must individualize further in patients in the remaining intermediate groups, I and II, in choosing the most appropriate therapy. Future advances upon understanding the molecular details of the MDS clone should ultimately improve the care of patients with MDS.
When Does the Responsibility of Our Care End: Bereavement
Authors: Penson Richard T. , Green Kara M. , Chabner Bruce A. , Lynch Thomas J. 
Published: February 2020

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Understand the effect of grief on the bereaved and on staff.Understand the responsibilities of compassionate cancer care.Recognize the resources available for uncomplicated and complicated grief.Access and take the CME test online and receive one hour of AMA PRA category 1 credit in Risk Management at CME.TheOncologist.comShortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. 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 sustenance to 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.Two vignettes are presented of a caregiver's response to the death of a patient, contrasting the extremes of involved compassion for the family and fractured relationships. Grief for loss is an inevitable part of life and a common part of cancer care. Support of the bereaved may be one of the hardest tasks for cancer care professionals, who are confronted with the limits of modern medicine. There is a responsibility to provide grieving families with support and care; care that goes beyond the death. A compassionate response helps both those who suffer and those who care. Complicated and uncomplicated bereavement, grief reactions, resources for bereavement counseling, and the role of condolence letters are reviewed.
Integrated, Multidisciplinary Management of Pulmonary Nodules Can Streamline Care and Improve Adherence to Recommendations
Authors: Roberts Thomas J. , Lennes Inga T. , Hawari Saif , Sequist Lecia V. , Park Elyse R. , Willers Henning , Frank Angela , Gaissert Henning , Shepard Jo-Anne , Ryan David 
Published: February 2020

Abstract

Every year millions of pulmonary nodules are discovered incidentally and through lung cancer screening programs. Management of these nodules is often suboptimal, with low follow-up rates and poor provider understanding of management approaches. There is an emerging body of literature about how to optimize management of pulmonary nodules. The Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) at Massachusetts General Hospital was founded in 2012 to manage pulmonary nodules via a multidisciplinary approach with optimized support staff. Recommendations from clinic providers and treatment details were recorded for all patients seen at the PNLCSC. Adherence to recommendations and outcomes were also tracked and reviewed. From October 2012 to September 2019, 1,136 patients were seen at the PNLCSC, each for a mean of 1.8 appointments (range, 1–10). A total of 356 procedures were recommended by the clinic and 271 patients were referred for surgery and/or radiation. The majority of interventions (74%) were recommended at the initial PNLCSC appointment. In total, 211 patients (19%) evaluated at the PNLCSC had pathologically confirmed pulmonary malignancies or were treated empirically with radiation. Among patients followed by the clinic, the adherence rate to clinic recommendations was 95%. This study shows how a multidisciplinary approach to pulmonary nodule management can streamline care and optimize follow-up. The PNLCSC provides a template that can be replicated in other health systems. It also provides an example of how multidisciplinary approaches can be applied to other complex conditions.

Implications for Practice
This work demonstrates how an integrated, multidisciplinary approach to management of pulmonary nodules can streamline patient care and improve adherence to provider recommendations. This approach has the potential to improve patient outcomes and reduce health care costs.
A Systematic Review of Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies
Authors: Cohen Julia W. , Akshintala Srivandana , Kane Eli , Gnanapragasam Helen , Widemann Brigitte C. , Steinberg Seth M. , Shah Nirali N. 
Published: February 2020

Abstract

Background
Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) &lt;10%. Recently, with an emphasis on targeted approaches, response rates may have changed. We analyzed outcomes of recent phase I pediatric oncology trials.

Materials and Methods
This was a systematic review of phase I pediatric oncology trials published in 2012–2017, identified through PubMed and EMBASE searches conducted on March 14, 2018. Selection criteria included full-text articles with a pediatric population, cancer diagnosis, and a dose escalation schema. Each publication was evaluated for patient characteristics, therapy type, trial design, toxicity, and response.

Results
Of 3,431 citations, 109 studies (2,713 patients) met eligibility criteria. Of these, 78 (72%) trials incorporated targeted therapies. Median age at enrollment/trial was 11 years (range 3–21 years). There were 2,471 patients (91%) evaluable for toxicity, of whom 300 (12.1%) experienced dose-limiting toxicity (DLT). Of 2,143 patients evaluable for response, 327 (15.3%) demonstrated an objective response. Forty-three (39%) trials had no objective responses. Nineteen trials (17%) had an ORR &gt;25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58).

Conclusion
Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target-specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials.

Implications for Practice
Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.
Weekly Chemotherapy of 5-Fluorouracil plus Cisplatin Concurrent with Radiotherapy for Esophageal Squamous Cell Carcinoma Patients with Postoperative Locoregional Recurrence: Results from a Phase II Study
Authors: Chen Baoqing , Li Qiwen , Li Qiaoqiao , Qiu Bo , Xi Mian , Liu Mengzhong , Hu Yonghong , Zhu Yujia 
Published: February 2020

Abstract

Lessons Learned
Weekly treatment with 5-fluorouracil and cisplatin, concurrent with radiotherapy, achieved promising response rates in patients with postoperative recurrent esophageal squamous cell carcinoma. Superior toxicity results were also found.

Background
Concurrent chemoradiotherapy (CCRT) is one of the treatment strategies for patients with esophageal squamous cell carcinoma (ESCC) with postoperative locoregional recurrence. However, the once every 3 weeks chemotherapy regimen causes a high incidence of toxicity. The aim of this study was to evaluate the efficacy and toxicity of weekly 5-fluorouracil (5-FU) and cisplatin concurrent with radiotherapy in postoperative locoregional recurrent ESCC.

Materials and Methods
Patients received four weekly chemotherapy cycles of cisplatin (25 mg/m2, day 1) plus 5-FU (1,176 mg/m2, day 1–3), and concurrent with radiotherapy (50.4–60 Gy). The primary endpoint was objective response rate (ORR). Secondary objectives were toxicity, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results
Between January 2013 and December 2015, 48 patients were enrolled. The ORR was 68.8% (12 patients with complete response, 21 patients with partial response), with DCR 68.8%. No treatment-related grade 4 adverse events occurred. Grade 3 hematologic toxicities were observed in eight (17%) patients. Grade 3 vomiting or esophagitis occurred in four (8%) patients each. The median PFS and OS were 13.94 months (95% confidence interval [CI], 0.75–51.05) and 27.43 months (95% CI, 5.278–49.58; Fig. 1).

Conclusion
Weekly 5-FU and cisplatin concurrent with radiotherapy achieved a promising response rate and improved toxicity in patients with postoperative locoregional recurrent ESCC.
Extending the Platinum-Free Interval in Recurrent Ovarian Cancer: The Role of Topotecan in Second-Line Chemotherapy
Authors: Bookman Michael A. 
Published: February 2020

Abstract
Although the combination of platinum and paclitaxel offers effective chemotherapy for advanced ovarian cancer, the majority of women will eventually relapse with development of drug-resistant disease. Topotecan is the most extensively studied agent currently available for management of recurrent ovarian cancer and has been approved by the FDA for that particular indication. Early use of topotecan offers an effective and tolerable strategy that can prolong the platinum-free interval and optimize subsequent retreatment with platinum.