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Empiric Antifungal Therapy for the Neutropenic PatientAmong the most significant complications a neutropenic patient can experience is an invasive fungal infection. In this issue of Oncology, Drs. Wingard and Leather thoroughly review the epidemiology, clinical presentation, and empiric treatment of these infections, particularly those associated with Candida and Aspergillus. They emphasize the need for better methods of identifying individuals at high-risk for invasive fungal infections because those individuals are more likely to benefit from antifungal prophylaxis or empiric therapy. The goal of such a targeted approach is to limit the amount of antifungal agents given, thereby decreasing the number of adverse effects and diminishing the selection of antifungal-resistant species.[1]
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Commentary (Neuwelt/Dahlborg): Current Management of Primary Central Nervous System LymphomaDr. DeAngelis has written a succinct and accurate assessment of management of primary central nervous system lymphoma. Non-AIDS-related primary central nervous system lymphoma is a rare, highly malignant primary brain tumor. However, its incidence is increasing, as are AIDS-related tumors of this type. Patients with primary central nervous system lymphoma usually have widespread infiltration throughout the brain, rendering aggressive resection of no benefit. There is a significant incidence of leptomeningeal and ocular involvement (the latter a "sanctuary site," thus posing a particular therapeutic dilemma).
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Use of Transcription Factors as Agents and Targets for Drug DevelopmentCancer is a genetic disease wherein mutations of growth regulatory genes result in abnormal proliferative capacity, recognized clinically as the occurrence of a malignant tumor. Transcription factors govern the expression of genes, be they "housekeeping" or regulatory. These factors organize the first crucial step in establishing the function of the gene, namely, the transcription of information in DNA into messenger RNA (mRNA). Translation of mRNA results in the synthesis of the oncogenic protein. Hence, the design of therapeutic agents targeted at transcription factors regulating the initial flow of "bad" information from "damaged" genes should be the ultimate goal of efforts to develop new weapons in the therapeutic armamentarium of the oncologist and, indeed, the general internist.
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Treatment Response and Duration of Therapy in Transplant-Ineligible NDMMClosing out their module on transplant-ineligible NDMM management, expert panelists consider best practices regarding duration of therapy and adjustments to drug regimens.
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Edward B. Garon, MD, Discusses Outcomes in NSCLC With Dato-DXd From TROPION-PanTumor01CancerNetwork® sat down with Edward B. Garon, MD, at the 2021 World Conference on Lung Cancer to talk about key findings with datopotamab deruxtecan therapy in patients with non–small cell lung cancer and other ongoing trials.
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An Alpha Edge?One would hope that survival data from at least one more phase III or phase IV clinical trial will convincingly show a prolongation of survival due to treatment with Alpharadin. This will not be inexpensive therapy.
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Malignant Gliomas in Older Adults With Poor Prognostic SignsThe median survival time of adults with supratentorial malignant glioma treated in clinical studies with surgery, 6 weeks of external-beam radiotherapy, and carmustine (BiCNU) is approximately 1 year. This poor survival time
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Palliative Care and Oncology: Integration Leads to Better CarePatients with advanced progressive cancer require care plans that address their physical, emotional, and psychosocial needs, as well as their goals of care.
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The Adjuvant Treatment of Stage III Colon Cancer: Might Less Be More?In this article, we review the findings of the IDEA study and discuss the optimal duration of oxaliplatin-based adjuvant chemotherapy using patient-based risk factors.
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A 60-Year-Old Man With Progressive Anemia While Receiving Checkpoint Blockade Therapy for Relapsed MyelofibrosisA 60-year-old man with a history of coronary artery disease and JAK2 V617F–positive polycythemia vera presented to our bone marrow transplantation clinic with progressive fatigue, splenomegaly, and cytopenias.
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Imaging Tumoral Hypoxia: Oxygen Concentrations and BeyondThe role of hypoxia as a key determinant of outcome for human cancers has encouraged efforts to noninvasively detect and localize regions of poor oxygenation in tumors. In this review, we will summarize existing and developing techniques for imaging tumoral hypoxia. A brief review of the biology of tumor oxygenation and its effect on tumor cells will be provided initially. We will then describe existing methods for measurement of tissue oxygenation status. An overview of emerging molecular imaging techniques based on radiolabeled hypoxic markers such as misonidazole or hypoxia-related genes and proteins will then be given, and the usefulness of these approaches toward targeting hypoxia directly will be assessed. Finally, we will evaluate the clinical potential of oxygen- and molecular-specific techniques for imaging hypoxia, and discuss how these methods will individually and collectively advance oncology.
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Cisplatin, Fluorouracil, Celecoxib, and RT in Resectable Esophageal Cancer: Preliminary ResultsEsophageal cancer frequently expresses cyclooxygenase-2 (COX-2)enzyme. In preclinical studies, COX-2 inhibition results in decreasedcell proliferation and potentiation of chemotherapy and radiation. Wereport preliminary results of a phase II study conducted by the HoosierOncology Group in patients with potentially resectable esophageal cancer.All patients received cisplatin at 75 mg/m2 given on days 1 and 29and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) wasadministered at 200 mg orally twice daily beginning on day 1 untilsurgery and then at 400 mg orally twice daily until disease progressionor unexpected toxicities, or for a maximum of 5 years. Esophagectomywas performed 4 to 6 weeks after completion of chemoradiation. Theprimary study end point was pathologic complete response (pCR). Secondaryend points included response rate, toxicity, overall survival, andcorrelation between COX-2 expression and pCR. Thirty-one patientswere enrolled from March 2001 to July 2002. Respective grade 3/4 toxicitieswere experienced by 58%/19% of patients, and consisted of granulocytopenia(16%), nausea/vomiting (16%), esophagitis (10%), dehydration(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)required initiation of enteral feedings. There have been seven deathsso far, resulting from postoperative complications (2), pulmonary embolism(1), pneumonia (1), and progressive disease (3). Of the 22 patients(71%) who underwent surgery, 5 had pCR (22%). We concludethat the addition of celecoxib to chemoradiation is well tolerated. ThepCR rate of 22% in this study is similar to that reported with the use ofpreoperative chemoradiation in other trials. Further follow-up is necessaryto assess the impact of maintenance therapy with celecoxib onoverall survival.
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Oral Complications of Cancer TherapyThe mouth is a frequent site of complications arising from drug or radiation cancer therapy, with mucositis, xerostomia, osteoradionecrosis, and local infections being the most common. From the standpoint of dose
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Transoral Robotic Surgery (TORS): The Natural Evolution of Endoscopic Head and Neck SurgeryThe article presented by Bhayani, Holsinger, and Lai thoroughly evaluates the emergence of transoral robotic surgery (TORS) as a technique in the field of otolaryngology. Transoral approaches to the upper aerodigestive tract, whether for diagnostic or therapeutic purposes, represent core tenets of the discipline and formed one of the bases for the inception of the specialty. Innovations and refinements in optics and materials have steadily increased the view, reach, and, consequently the effectiveness of the endoscopic surgeon with each passing decade. In the past thirty years, the introduction of the laser has further enhanced the capabilities of the surgeon, augmenting treatment options beyond open tumor resection and chemoradiation. The introduction of the daVinci robot is an incremental step in the development of techniques that have been evolving over the past one hundred and twenty years.
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Commentary (Lee): Current Management of Acute Lymphoblastic Leukemia in AdultsOng and Larson provide an excellent review of acute lymphoblastic leukemia (ALL) in adults. They thoroughly discuss such basic issues as the diagnosis and classification of ALL, prognostic factors, and the principles of treatment. They also discuss specific problems that arise, such as the treatment of ALL in the elderly and in those with Philadelphia chromosome-positive ALL. In addition, the authors comment on areas that do not yet have fully defined roles in treatment, such as the detection of minimal residual disease and various methods of admin-istering high-dose chemotherapy supported by allogeneic or autologous progenitor cells obtained from blood or marrow. Their views, as expressed in this paper, are reasonable and supported by appropriate references. This review will therefore expand on and underline comments made by the authors in several areas.
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Targeted Therapy for Mutation-Driven Metastatic Non–Small-Cell Lung Cancer: Considerations for ALK-Rearranged TumorsIn this article, important concepts in the molecular testing of non–small-cell lung cancer are highlighted.
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Use of IP Chemotherapy in Ovarian Cancer: The Critical QuestionsThe article by Dr. Echarri Gonzalez and her colleagues regarding intraperitoneal (IP) chemotherapy for women with epithelial ovarian cancer provides a comprehensive yet practical review of the critical questions surrounding the use of IP chemotherapy.
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Irinotecan/Gemcitabine Followed by Twice-Weekly Gemcitabine/Radiation in Locally Advanced Pancreatic CancerEarly clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.
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Squamous Cell Carcinoma of the Anal MarginBased on our experience and a review of the literature, we conclude that superficial, well- to moderately differentiated T1 cancers of the anal margin may be successfully treated with radiotherapy alone or local
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N+, M0 Prostate Cancer: Local Therapy for Systemic DiseaseNode-positive prostate cancer without distant metastases (T any, N+, M0) currently is encountered rarely, primarily because of the shift to diagnosis at earlier stages, a result of widespread PSA testing.
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Active Surveillance for African-American Men With Prostate Cancer: Proceed With CautionActive surveillance seems to be generally safe, yet African-American men tend to have more aggressive prostate cancers. Thus, it is imperative that we learn the characteristics and outcomes of African-American men considering surveillance.
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Hyperthermia as a Treatment for Bladder CancerModern cancer care is characterized by a focus on organ-sparing multi-modal treatments. In the case of non–muscle-invasive bladder cancer this is particularly true; treatment is focused on reducing the frequency of low-risk recurrences and preventing high-risk progression. Deep regional hyperthermia is an oncologic therapeutic modality that can help achieve these two goals. The combination of hyperthermia with chemotherapy and radiotherapy has improved patient outcomes in several tumor types. In this review, we highlight the biology of therapeutic fever-range hyperthermia, discuss how hyperthermia is administered and dosed, demonstrate how heat can be added to other treatment regimens, and summarize the data supporting the role of hyperthermia in the management of bladder cancer.
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Outwitting the Blood-Brain BarrierThe blood-brain barrier and the blood-cerebrospinal fluid barrier are major physical impediments to therapeutics targeting central nervous system neoplasms. We review this topic from the perspective of a group whose focus is on the neurovascular unit.
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The Information Age, Cyberspace, and CancerOncologists and their patients are facing disruptive changes in healthcare, research, and communication. This dramatic increase in the quantity and quality has changed our lives forever. However, many of us remain frustrated with our inability to control this information overload.
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Prostate Cancer Clinical Trials of the Southwest Oncology GroupThe changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies. [ONCOLOGY 11(8):1155-1170, 1997]
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Commentary (Laws): Current Management of MeningiomasDr. DeMonte has used an interesting case report to provide an excellent summary of the state of the art in the management of meningiomas of the brain.
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Face-Off: Award CeremonyFollowing a comprehensive debate on the treatment of patients with non–small cell lung cancer, Edward Kim, MD, presents the winning team with the title of victors of this CancerNetwork® Face-Off event.
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Metastatic Breast CancerIn 1995, it is projected that there will be 183,400 new cases of breast cancer and 46,240 deaths from the disease, despite an emphasis on early detection [1]. Fewer than 10% of patients will present with metastatic disease, but nearly 50% of newly diagnosed patients may eventually develop it. Unfortunately, advanced breast cancer is incurable. In a classic study of untreated patients, the median survival was 2.7 years from the onset of symptoms [2].
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Cardiovascular Risk Associated With Androgen Deprivation TherapyProstate cancer is the second leading cause of cancer-related death among men in the United States.[1] Androgen deprivation therapy (ADT) is a common treatment for prostate cancer. ADT includes gonadotropin-releasing hormone (GnRH) agonists (leuprolide, goserelin, triptorelin), bilateral orchiectomy, and anti-androgen receptor blockers such as flutamide and bicalutamide. Several studies have now shown conflicting evidence that anti-androgen therapy may lead to increased cardiovascular morbidity and mortality.[2-5] None of these studies has provided conclusive evidence for causality or a direct link to cardiovascular disease, but they have proposed that therapy side-effects increase parameters that are similar to those of the metabolic syndrome.
