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Targeted Therapy: an Evolving Concept in Esophageal AdenocarcinomaEsophageal adenocarcinoma (EAC) affects approximately 11,000 persons per year in the United States, is increasing in incidence, and is associated with an exceptionally high mortality rate.[1-4] In this issue of ONCOLOGY, Krasna reviews the role of multimodality therapy in the treatment of EAC. Poor outcome in patients with EAC is reflective of both deficiencies in early detection and the inadequacy of available therapies across stages.
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Weighing the Evidence for Immune Therapy and Targeted Therapy in Renal Cancer and MelanomaUltimately, as agents in both VEGF-targeted and immunotherapy classes with lower toxicity rates are developed, questions of combination and sequence will inspire clinical investigations of strategies that, it is hoped, will maximize both the quantity and quality of life for patients with RCC. Melanoma therapy drug development continues to lead the way with regard to what is therapeutically possible with immunotherapy-and suggests that HD IL-2 continues to be relevant in today’s treatment landscape.
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Sharp Rise in Mastectomy in Early-Stage Breast CancerA retrospective cohort study of women treated for early-stage breast cancer has confirmed rising trends in the proportion of patients who undergo mastectomy.
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Cancer Care and Accountable Care Organizations: The Unknown Patient Experience LandscapeACOs can provide the structure, but it’s up to the stakeholders to establish mutually agreeable goals for this new care delivery model. Achieving these goals will require a different set of dialogues and conversations among stakeholders, and patients and their advocates must have seats at the table.
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Infusional 5-FU, Folinic Acid, Paclitaxel, and Cisplatin for MetastaticOur phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic
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Cervical Cancer: Issues of Sexuality and FertilityCervical cancer rates have fallen in the United States; regardless, thedisease remains a significant concern for women, especially those whoare premenopausal. The management of cervical cancer is dependenton stage of disease at diagnosis, and specific needs emerge for patientsboth during and following treatment. Over the past decade, the focus hasbeen to maintain adequate tumor control while reducing long-termnegative consequences. However, problems with sexuality and fertilitypersist for women treated for cervical cancer despite these advances.Sexual dysfunction following treatment for gynecologic cancer hasbeen well documented in the literature, and recent studies demonstratethe success of brief psychosexual interventions. Treatment of sexualdifficulties in cancer patients can be achieved through the provision ofinformation, support, and symptom management, ideally as part of asexual health program. Resources are not always available to developsuch a program. However, medical professionals can identify individualsand organizations with expertise in treating sexual and fertilityconcerns, which can be provided to their patients, making help withthese problems more accessible as needs arise.
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Morbidity of Contemporary Radical Retropubic Prostatectomy for Localized Prostate CancerComplication rates in 1,000 consecutive patients who underwent radical retropubic prostatectomy for clinically localized prostate cancer between November 1989 and January 1992 were assessed and compared to complication rates in a historical group of patients operated on by primarily the same surgeons prior to 1987. In the contemporary series, there were no operative deaths, only 22% of patients required blood transfusion, and only six (0.6%) patients suffered rectal injuries. Early complications, including myocardial infarction, pulmonary embolism, bacteremia, and wound infection, occurred in less than 1% of patients. Vesical neck contracture, the most common late complication, developed in 87 patients (8.7%). At 1 year post-surgery, 80% of patients were completely continent, and fewer than 1% were totally incontinent. [ONCOLOGY 9(5):379-389, 1995]
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Systemic Approaches for Multifocal Bronchioloalveolar Carcinoma: Is There an Appropriate Target?Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non–small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas-and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.
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Endoscopic Diagnosis and Management of Gastrointestinal MalignancyThe endoscopic diagnosis, staging, and therapy of gastrointestinal (GI) malignancies has advanced rapidly and dramatically over the past 15 years. Video-endoscopy has generally replaced fiberoptic endoscopy, and the digitally based fidelity, sharper resolution, and improved magnification of the video-endoscopic image offers a potentially better approach for the evaluation of mucosal abnormalities.
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Thromboembolic Complications of Malignancy: Part 2Thromboembolism affects many patients with solid tumors and clonalhematologic malignancies. Thromboprophylaxis with low-molecularweightheparin (LMWH) is indicated for surgery and other high-risksituations, but not routinely for central venous catheters or nonsurgical,ambulatory management. Thrombotic events require full anticoagulationfor the duration of active disease and/or the prothromboticstimulus. LMWHs are safe and more effective than both unfractionatedheparin for initial therapy and warfarin for secondary prevention. Antiinflammatoryand antiangiogenic properties might account for thisadvantage and for a survival benefit of chronic LMWH in subgroupsof cancer patients. Ongoing studies are characterizing the cost-effectivenessand antitumor mechanisms of LMWHs, the potential utility ofnewer anticoagulants, and the ability of predictive models to identifyhigh-risk candidates for thromboprophylaxis.
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Commentary (Meyers): Systemic Treatments for Advanced Cutaneous MelanomaThe history of systemic treatments for advanced cutaneous melanoma, which is reviewed thoroughly in the paper by Anderson et al, can best be characterized as a series of unrealized hopes.
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PSA Screening: Good Evidence Shows Little Benefit, Significant HarmsThe Task Force’s recommendation against PSA screening for prostate cancer is based on the best available science and the knowledge that, while we all want to prevent suffering and death from prostate cancer, PSA screening simply does not get us there.
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Stereotactic Radiation Therapy Combined With Immunotherapy: Augmenting the Role of Radiation in Local and Systemic TreatmentIn this review we detail the rationale supporting a combination of immunotherapy and stereotactic radiation. Additionally, we discuss the evidence for the immune stimulatory effects of focused radiation and the role that radiation may play in enhancing the systemic treatment effects of immunotherapy.
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Ipilimumab for Advanced Melanoma: Let’s Not Throw Caution to the WindsThe authors provide a timely and relevant review of the role that the immune system plays in regulating tumor growth and how immune modulation can alter tumor response. This review follows from the recently published phase III trial of ipilimumab,[1] a monoclonal antibody to cytotoxic T-lymphocyte antigen 4 (CTLA-4) and the first therapy in several decades to produce prolonged overall survival (OS) in patients with metastatic melanoma. While this outcome underscores the importance of this therapy in treating metastatic melanoma, its clinical applicability, at least on a widespread level, necessitates further exploration.
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Use of Hematopoietic Hormones for Bone Marrow Defects in AIDSAboulafia provides an extensive review of the occurrence of and treatments for bone marrow disorders that complicate HIV infection and AIDS. Understanding of the pathogenesis of these disorders is increasing, and the availability of recombinant colony-stimulating factors (CSFs) has, in many ways, facilitated the treatment of HIV-1 infection and its complications. Nonetheless, numerous critical questions remain regarding the optimal use of these expensive and powerful reagents.
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State of CML TreatmentsIn this interview, we discuss the current state of therapies available in treating CML patients and the role of newer agents.
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Second-Guessing the FDA: CMS’s Expanding Regulatory RoleNothing gets biopharma policy watchers more worked up than the possibility that the Centers for Medicare & Medicaid Services (CMS) will second-guess FDA approval decisions. In reality, though, CMS often has no choice but to apply its own interpretation to issues that also fall under the FDA’s jurisdiction-and implementation of the health care reform is bringing more of those cases to the fore.
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Management of Benign and Aggressive Intracranial MeningiomasBenign and aggressive intracranial meningiomas, as the authors state, are seemingly simple tumors (even with benign histology) that can behave in a clinically malignant fashion solely by location. Clinicians with experience in the management of patients with aggressive, recurrent, or malignant meningiomas are all too well aware of the difficulties of recommending effective therapy beyond surgery and radiation therapy. Clearly, there is much room for improvement in the treatment of recurrent or malignant meningiomas with local or systemic chemotherapy and/or biologic therapies.
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Assessing the Impact of Chemotherapy on Tumor- Related Symptoms in Advanced Colorectal CancerIn all patients with advanced colorectal cancer, disease eventually progresses following fluorouracil (5-FU) therapy, with a worsening of disease-related symptoms and quality of life (QOL). Irinotecan (CPT-11[Camptosar])
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The Pathways of Tomorrow: What Does the Future Hold for the Treatment of Colorectal Cancer?The currently available therapies for colorectal cancer have led to a significant increase in survival, but the majority of patients with advanced disease progress and eventually die of their disease. This is a particularly frustrating scenario when a patient experiences a complete remission, only to recur with refractory disease.
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Cancer Management Chapter 9: Esophageal cancerAlthough still relatively uncommon in Western countries, esophageal cancer is fatal in the vast majority of cases. In the United States, an estimated 16,470 new cases will be diagnosed in the year 2009, and 14,530 deaths will result from the disease. This high percentage of deaths rivals that of pancreatic cancer and is more than four times that of rectal cancer.
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Commentary (Needle): Long-Term Survival of Children with Brain TumorsThe diagnosis and treatment of children with brain tumors has changed radically over the last 50 years. Cross-sectional imaging, CT and MRI, has displaced angiography and pneumoencephalography. These newer imaging modalities have facilitated early diagnosis, preoperative planning, and surgical approach, resulting in an increased likelihood of achieving complete surgical extirpation. The operating microscope has improved the experienced surgeon's ability to discriminate between tumor and normal brain, making radical resection more frequent. Chemotherapy has been introduced into the arsenal of the neuro-oncologist, albeit with only modest success. The one nearly constant treatment modality has been external-beam irradiation.
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Tools for Measuring and Improving the Quality of Oncology Care: The Quality Oncology Practice Initiative (QOPI®) and the QOPI Certification ProgramThe American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI®) is a voluntary program designed to assess and improve processes of care in oncology practices.
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Latest Immunotherapy Research in Treating Colorectal CancerIn this interview we discuss the CheckMate 142 trial, which looked at nivolumab and ipilimumab for the treatment of metastatic colorectal cancer.
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Managing a Small Recurrence in the Previously Irradiated BreastBreast cancer is the most common newly diagnosed malignancy among American women. In 2008, an estimated 182,460 new cases of invasive breast cancer, and an additional 67,770 cases of in situ cancer were diagnosed. Approximately 40,480 women will die from breast cancer each year.
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Commentary (Perry): Cancer Management in Patients With End-Stage Renal DiseaseThe increasing number of patientson chronic renal replacementtherapy translates to additionalpatients living long enoughto develop a malignancy. For the mostpart this population will also be elderly,adding the nuances associated withpracticing oncology in a geriatric population.As discussed by Eneman andPhillips, the use of chemotherapeuticagents in patients with end-stage renaldisease (ESRD) is complicated byboth practical and ethical issues.
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The Best Treatment for Diffuse Large B-Cell Lymphoma: A German PerspectiveWhile some improvement was achieved by adding etoposide and shortening the treatment intervals from 3 to 2 weeks (CHOEP-14), best results in young good-prognosis patients (age-adjusted International Prognostic Index [IPI] = 0,1) have been achieved with six cycles of CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone)-like chemotherapy in combination with the anti-CD20 antibody rituximab (Rituxan). The role of additional radiotherapy in this setting remains to be determined. With this approach, 2-year eventfree survival rates of > 90% and overall survival of > 95% can be achieved in a very favorable subgroup (patients without IPI risk factor and no bulky disease), while further improvement is warranted for the less favorable subgroup (event-free survival only 77%). For young poorprognosis patients (age-adjusted IPI ≥ 2), the 5-year survival is around 50%, and progress has not been convincingly and specifically demonstrated in these patients. Ongoing studies will show whether dose-dense conventional or high-dose chemotherapy regimens requiring stem cell support in combination with rituximab will result in similar improvements of outcome as has been reported recently for young patients with good-prognosis aggressive lymphoma. In elderly patients, CHOP interval reduction from 3 to 2 weeks (CHOP-14) and the addition of rituximab to CHOP-21 achieved similar improvements in outcome. The ongoing RICOVER-60 (rituximab with CHOP over 60) trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) evaluates whether the combination of both approaches (R-CHOP-14) can further improve the prognosis of elderly patients.
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AACR: Insulin Signaling and Cancer Development, ProgressionAhead of the 2015 AACR Annual Meeting we discuss how insulin resistance relates to current cancer therapies.
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European Experience With Oral Solution and Intravenous ItraconazoleThe availability of an improved oral solution and an intravenous (IV) formulation of itraconazole (Sporanox) promises to have an effect on prevention and treatment of fungal infection in immunocompromised patients. Use of itraconazole in neutropenic patients with hematologic malignancies has been evaluated in a number of European studies. Treatment with IV followed by oral itraconazole resulted in response or stable disease in two-thirds of patients with invasive pulmonary aspergillosis. Empiric treatment with IV followed by oral solution itraconazole was at least as effective as, and significantly less toxic than, amphotericin B. Several studies of oral solution prophylaxis indicate effectiveness in prevention of fungal infection. Oral solution and IV itraconazole are useful in a variety of situations in prophylaxis, empiric therapy, and treatment of probable/confirmed infection. Itraconazole exhibits a broad spectrum of activity against Aspergillus and Candida species. It has potential advantages over fluconazole (Diflucan), which does not exhibit in vitro activity against Aspergillus and most non-albicans Candida species, and amphotericin B, which is associated with a high incidence of toxicity. Aggressive use of itraconazole and amphotericin B preparations in treatment of fungal infection at Royal Free Hospital may have reduced mortality associated with aspergillosis. [ONCOLOGY 15(Suppl 9):27-32, 2001]
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Radiotherapeutic Management of MedulloblastomaDr. Paulino provides a concise yet complete review of the radiotherapeutic management of patients with medulloblastoma. Radiotherapy treatment planning for medulloblastoma is complex, requires considerable attention to detail, and remains the subject of debate and clinical research. Clearly, this is an area of neuro-oncology in which multidisciplinary research has played a significant role in improving survival for children and young adults with this disease.
