ONCOLOGY Vol 24 No 6

Oncologists often do not give honest prognostic and treatment-effect information to patients with advanced disease, trying not to “take away hope.” The authors, however, find that hope is maintained when patients with advanced cancer are given truthful prognostic and treatment information, even when the news is bad.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF’s nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.

The article entitled “Diagnosis and Management of Mycosis Fungoides” by Shira Galper, Benjamin Smith, and Lynn Wilson is an excellent contemporary summary of the workup and management of mycosis fungoides (MF) and its leukemia variant, Sézary syndrome (SS). In their discussion of the diagnosis and staging of MF and SS, the authors include a discussion of proposed revisions by the International Society for Cutaneous Lymphoma and the European Organisation for the Research and Treatment of Cancer (ISCL/EORTC) which seek to identify prognostic subgroups. In addition, there is a complete overview of the various treatment options for management of MF and SS. This treatment overview closely parallels the 2010 National Comprehensive Cancer Network (NCCN) Practice Guidelines for MF and SS.

Galper et al. should be commended for their concise and useful review of the diagnosis and management of mycosis fungoides (MF). It is notable that all of the authors are radiation oncologists. While the reader may expect a radiation oncologist’s perspective on the management of mycosis fungoides, their review goes beyond highlighting the various radiation techniques used in the treatment of MF. It highlights the major diagnostic dilemmas when evaluating patients with skin lesions that eventually are diagnosed as MF or its leukemic counterpart, Sézary syndrome (SS). It also stresses the importance of a multidisciplinary approach in diagnosing and caring for MF patients involving dermatology, dermatopathology, radiation oncology, and hematology/oncology, and provides a concise review of the treatment options in the MF and SS armamentarium. Navigating these options requires a good understanding of the natural history of the disease, the side effects of treatment, the expected response rates of treatment, the median time to response, the patient’s comorbid conditions, and goals of care.

Authors of a new report, commissioned by the National Cancer Institute (NCI) and conducted by the Institute of Medicine (IOM) has found that inefficient management, overly complicated government oversight, and inadequate funding hamper the ability of the National Cancer Institute’s Clinical Trials Cooperative Group Program to design and run studies that properly answer critical questions about new therapies.

Additional data from the phase III IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) clinical trial showed evidence of immune responses in patients treated with sipuleucel-T (PROVENGE), supporting its proposed mechanism of action. The study results were presented at the American Association for Cancer Research (AACR) 101st Annual Meeting, held April 17–21, 2010 in Washington, DC.

Results of a new study published in the Annals of Internal Medicine [Ann Intern Med 152:505-512, 2010] indicate that the risk for false-positive results of CT lung cancer screening tests is substantial. Led by Jennifer M. Croswell, MD, researchers from NCI sought to quantify the cumulative risk in a 1- or 2-year lung cancer screening exam, based on at least one false-positive finding.

Bone health is a critical issue in the management of women with breast cancer. Many women who develop breast cancer are postmenopausal, which already predisposes them to osteoporosis. Systemic treatments for breast cancer, including chemotherapy and endocrine therapy, decrease circulating levels of estrogen in both pre- and postmenopausal women, further accelerating the natural process of bone loss. The primary concern in breast cancer patients is that this accelerated bone loss, known as cancer treatment–induced bone loss (CTIBL), will lead to an increase in fractures, chronic pain, and loss of mobility. Bisphosphonates are highly effective at slowing the rate of bone loss in postmenopausal women with osteoporosis and at preventing skeletal-related events in women with metastatic breast cancer. Many studies are now focusing on the role of bisphosphonates in preventing CTIBL in the adjuvant setting. Both oral and intravenous bisphosphonates have shown promising activity in preventing CTIBL in patients receiving chemotherapy or hormonal therapy. In addition, emerging data indicate that the use of bisphosphonates in the adjuvant setting may prevent disease recurrence and prolong survival. Data from a number of ongoing trials will further elucidate the role of bisphosphonates in the adjuvant setting over the next few years.

Kilbridge correctly points out that comparative effectiveness research (CER) does not require cost data. It should also be pointed out, however, that the composition of the quality-adjusted life-year (QALY) gain of one intervention over another-whether the QALY gain is achieved mainly in the dimension of longevity or in the dimension of quality of life-has real consequences in terms of comparative costs of the interventions. Basically, a longevity increase entails additional consumption costs and additional labor earnings, essentially negative costs, during the extended life that should be included in the “cost” of an intervention.[1-3] Because labor earnings tend to be negligible relative to consumption costs toward the end of one’s life, due to sickness or retirement, failure to incorporate consumption costs and labor earnings into the comparative costs of two interventions generates a bias in favor of the intervention with the larger longevity effect.

Turmeric, a perennial herb prevalent in South Asia, is ubiquitous in Asian and Middle Eastern cooking. It is also used in Ayurveda and traditional Chinese medicine to treat inflammation, burns, and disorders of the digestive system.

Recently, the American Recovery and Reinvestment Act (ARRA) set aside $1.1 billion for comparative effectiveness research (CER) to investigate what healthcare strategies and interventions offer the greatest benefits to individual patients and the population as a whole. The Institute of Medicine has identified CER in cancer care as a high priority research focus for ARRA funding. The ability to measure quality of life will be central to CER in oncology because survival and disease-free survival do not adequately capture outcomes important to policy makers, physicians, and patients. There are two ways to measure quality of life: descriptive health status and patient preference weights (utilities). However, only patient preference weights can be incorporated into the economic analysis of medical resources and be used in the calculation of quality-adjusted life-years (QALYs). Some of the advantages and limitations inherent in measuring quality of life with descriptive health status and patient preference weights are discussed. Both types of measurements face health literacy barriers to their application in underserved populations, an important concern for CER in all medical fields.

A majority of the more than 190,000 women diagnosed with breast cancer each year in the US[1] will receive some form of adjuvant therapy. Many breast cancer treatments cause decreases in circulating estrogen levels, which in turn can have a significant effect on bone mineral density; this condition is known as cancer treatment-induced bone loss (CTIBL). In this issue of ONCOLOGY, Reeder and Brufsky review the role of bisphosphonates in the setting of adjuvant breast cancer treatment. Both oral and intravenous bisphosphonates are effective in the prevention and treatment of CTIBL, and emerging data suggest that adjuvant bisphosphonate therapy may also affect breast cancer recurrence and survival. In considering the role of these medicines in early stage breast cancer, however, a number of important questions remain.

Breast cancer is the most common noncutaneous cancer among women.[1] In 2009, an estimated 190,000 new cases occurred in the US. The 5-year survival rate for early-stage breast cancer has improved from approximately 63% in the early 1960s to almost 90% today, mainly as a result of early detection and treatment.[2] The improvement in survival from breast cancer treatments, however, which include chemotherapy, endocrine therapy, and/or ovarian ablation, does not come without the cost of potentially significant effects on bone mineral density (BMD).[3-5] The risk of having low bone mass increases significantly with age, as does the risk of developing breast cancer; consequently, the two diagnoses often overlap in the same individual. Additionally, women with breast cancer may be at increased risk for osteoporosis due to the effect on bone of certain anticancer therapies. Hence, some women with breast cancer may be at increased risk of osteoporosis.

In this issue of Oncology, Dr. Kilbridge details the incorporation of nontraditional outcome measures in the evaluation of cancer therapies-the importance of which is underscored by the passage of the sweeping healthcare reform bill that will alter the landscape of healthcare delivery for years to come.