ONCOLOGY Vol 24 No 10

Bronchioloalveolar carcinoma (BAC) is a unique subtype of lung adenocarcinoma that has received increasing attention in recent years. Levy and colleagues have provided a comprehensive review of the clinical and pathologic characteristics of this disease, as well as the clinical evidence available to guide treatment of patients with BAC.

Red clover is a perennial herb traditionally used to treat skin conditions such as eczema and psoriasis, whooping cough, and respiratory problems. The isoflavones present in red clover have estrogen-like effects and have been the subject of intense research over the last decade. Data on red clover’s potential for reducing the symptoms of menopause and for decreasing the risk of breast cancer are inconclusive. Overuse of isoflavone supplements can increase the risk of hormone-sensitive cancer.

It appeared that the controversy surrounding the pros­tate cancer immunotherapy Provenge ended with FDA approval in April. But now Medicare is questioning whether the government should pay for the new therapy. The CMS decision is just as important to the biopharmaceutical indus­try as it is to Dendreon.

Here we present the case of a 3-year-old girl with generalized lymphadenopathy and fever, in whom the cause of the symptoms was initially thought to be infectious. Ultimately, however, anaplastic large cell lymphoma (ALCL) was diagnosed. Using this case as a backdrop, we discuss the wide range of systemic illnesses that the differential diagnosis of generalized lymphadenopathy encompasses.

Jacobson and LaCasce have provided a thorough review of post-transplant lymphoproliferative disorders (PTLDs), but the authors did not completely cover the field. While the article describes the development of lymphoid tumors related to Epstein-Barr virus (EBV) in patients who have received an organ transplant, it did not consider PTLDs developing after hematopoietic stem cell transplant, a condition also related to EBV but which is more aggressive. Not all PTLD cases are related to EBV, however, and as in patients with HIV (human immunodeficiency virus) infection or hereditary immune deficiency, other lymphoma subtypes may be observed, including T-cell lymphomas[1] (anaplastic large cell lymphoma,[2,3] hepatosplenic lymphoma[4]), indolent lymphomas[5]; and also Hodgkin lymphoma,[6,7] multiple myeloma,[8] or lymphoproliferative disorders associated with human herpes virus 8 infection.[9]

Post-transplant lymphoproliferative disorder (PTLD) is a common and serious complication of solid organ transplantation. It is a heterogeneous collection of diagnoses with varied clinical courses and outcomes. The majority of PTLD is Epstein-Barr virus (EBV)-driven as a result of loss of immune control of EBV-positive B lymphocytes. Risk factors for the development of PTLD thus reflect loss or absence of EBV immunity; they include younger age and pre-transplant EBV naivety, as well as the degree and type of immune suppression, type of organ transplantation, and time from transplantation. Identifying patients at risk for PTLD and developing strategies to prevent PTLD is the subject of much research, and the use of antiviral medications and EBV vaccines has yielded intriguing, albeit preliminary, results. As we learn more about the prognostic factors affecting outcome and the pathogenesis of individual diseases, we are better able to tailor therapy to the individual. Further clinical investigation, including randomized controlled trials, will be important in reaching this goal.

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies caused by the traditional risk factors of tobacco, alcohol, and poor oral hygiene, as well as more recently identified roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV).[1-3] We commend Kim and colleagues on their comprehensive review of the epidemiology of HNSCC. There has been a clear change in the epidemiology of HNSCC which has further accentuated differences in etiology, survival, and demographics among HNSCC patients. We will discuss several important nuances of this changing epidemiology, including the role of tobacco, race, sexual behavior, and gender, as well as HNSCC in nonsmokers and nondrinkers.

As outlined by Leslie Kim and colleagues in this issue of ONCOLOGY,[1] almost 650,000 new cases of head and neck cancer are identified and approximately 350,000 individuals die from this disease worldwide each year. Most cancers of the head and neck are squamous cell carcinomas and originate from one of five major sites: oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Traditionally, tobacco smoking and alcohol consumption have been considered to be the main risk factors for head and neck squamous cell carcinoma (HNSCC) and, thus far, most prevention strategies and public health messages have focused on these two factors. However, as described in the review by Kim et al., there is increasing evidence that, independent of tobacco and alcohol exposure, oral human papillomavirus (HPV) infection is a major risk factor for a specific subset of HNSCCs. We agree with the authors that this is an important public health concern, especially given the increasing prevalence of HPV infection in the US and Western Europe and our limited knowledge about the natural history of oral HPV infection. Here we summarize the role of HPV in HNSCC and discuss clinical implications.

In this issue of Oncology, Levy and colleagues provide a comprehensive review of bronchioloalveolar carcinoma [BAC], with a focus on the management of this rare disease, which represents 4% of all lung cancers.[1] The definition of BAC was revised by the World Health Organization (WHO) in 2004, with changes made to the diagnostic criteria and classification.[2] BAC was defined as an adenocarcinoma of the lung that grows in a lepidic fashion along the alveolar septa without invasion of stroma, blood vessels, or pleura. BAC has been sub-classified into three types: nonmucinous, mucinous, and mixed.

Characterizing the epidemiology of head and neck cancers is challenging and has received limited attention in the medical literature. Traditionally, 80%–90% of head and neck squamous cell carcinomas (HNSCCs) have been attributed to tobacco and alcohol use, but with growing public awareness and tobacco control efforts over the past few decades, there has been a downward trend in smoking prevalence in the US. There is also emerging evidence that human papillomavirus (HPV) is responsible for inconsistencies in HNSCC trends, with oncogenic HPV DNA found in approximately half of oropharyngeal cancers and in a high proportion of oropharyngeal cancers in nonsmokers and nondrinkers. The risk to HNSCC epidemiology is that whatever gains continue to be made in tobacco control may become lost in the increasing numbers of oropharyngeal cancers due to HPV. The purpose of this review is to explore the changing epidemiology of HNSCC, focusing on how it has been shaped by health policy and advocacy interventions and how it will continue to have public health implications in the future, particularly in considering preventive strategies against HPV. Given that the majority of HNSCCs are the result of exposure to preventable public health risks, more focus should be given to this area.

In this issue of ONCOLOGY, Jacobson and LaCasce present a complete review of the risk factors, prognosis, and treatment of post-transplantation lymphoproliferative disorders (PTLD) following hematopoietic stem cell transplant (SCT) and solid organ transplant (SOT). They aptly describe the continued relatively high rate of PTLD in transplant recipients; approximately 2% to 3% of all SOT subjects will ultimately develop this potentially fatal disorder, a rate that is more than 30 times higher than that in the general population.[1] Furthermore, lymphoproliferative diseases represent approximately 20% of all malignancies in SOT subjects, compared with ~5% in the general population.[2,3]

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.