Reviews & Analysis

The current tools of clinical risk assessment for medulloblastoma cannot sufficiently identify patients older than 3 years who require aggressive or less-intensive radiation treatment, but considerable effort has been made to improve clinical risk stratification. The current paradigm for stratifying patients for treatment is discussed and the authors highlight that an understanding of the biology of medulloblastoma will help improve clinical risk stratification that currently under treats and over treats a significant percentage of patients.

Single-modality therapy can be used with curative intent for locally confined disease. For the treatment of most solid tumors further improvement is achieved by combining the three standard treatment approaches: surgery, radiotherapy, and chemotherapy. This article reviews the chemoradiotherapy approach to loco-regional treatment with esophageal cancer as the disease focus. The authors present the molecular basis for the enhanced efficacy resulting from the use of concurrent chemoradiotherapy, and discuss how this mechanistic approach can be translated to the clinic.

ERα and ERβ are structurally and functionally distinct, but currently only ERα is used to guide clinicians. The authors of this Viewpoint discuss whether this strategy is sufficiently informative, and how outcome and tumor response to adjuvant hormonal therapy can be followed more effectively.

In this Viewpoint, Richard Kaplan asserts that phase II oncology trials could be improved using strategies such as adding a 'real-world' cohort, validating biomarkers across trials, utilizing factorial designs to answer several clinical questions simultaneously, and coordinating academic trial design on an international basis.

Papillary type 2 renal cell carcinoma (RCC) is part of the hereditary leiomyomatosis and renal cell carcinoma syndrome that is caused by a mutation in the fumarate hydratase (FH) gene. In this article, the authors present a tragic case of a young man who was diagnosed with papillary type 2 RCC and was managed with radical nephrectomy, immunotherapy, chemotherapy and surgical debulking. The article discusses the treatment and management of patients with renal manifestations of FH heterozygosity that are the most serious aspects of the syndrome, and underlines the need for genetic evaluation of patients and members of their families.

Although significant advances in primary and secondary cervical cancer prevention have been achieved, their true realization and ultimate impact on global disease outcomes will be affected by a number of complex and interrelated factors. One promising prophylactic HPV vaccine is available and others continue in development as primary cervical cancer prevention strategies in younger women. HPV testing is more sensitive and reproducible than cytology with colposcopy for the detection of precancerous and malignant lesions, and this review presents current advances and perspectives on HPV vaccines and HPV testing.

The successful introduction of genetically engineered human and chimeric immunoglobulin proteins has established monoclonal antibodies as a validated approach for treating malignancies. This review examines the optimal design of these agents, the lessons learned from clinical immunoconjugate development, and the promising agents in early preclinical and clinical development for the treatment of cancer.

It is clear that androgen receptor (AR) expression and signaling remains intact as the disease evolves from androgen sensitive cancer to classically termed hormone-refractory prostate cancer. Genetic and epigenetic changes allow prostate tumors to continue to rely on AR growth signaling and thus remain targets of 'hormonal' therapy. The development of new strategies and new drugs that more effectively abrogate AR signaling will likely result in significant clinical benefits. This article discusses AR structure, function and molecular changes in androgen-independent prostate cancer and reviews novel AR targeting compounds.

Legal barriers, restricted resources, lack of physician training, and physician and patient worries about potential opioid addiction can be barriers to effective and rational pain management in patients with cancer pain. Sebastiano Mercadante discusses these issues, as well as suggesting interventions for improving care.

Observations that CTLA4 has a key role in regulating immune responses mediated via T cells have led to therapeutic approaches targeting this inhibitory pathway for tumor immunotherapy. It is possible that combining anti-CTLA4 antibodies with a vaccine may help to direct immune responses toward target antigens, enhancing clinical efficacy and perhaps reducing treatment-related adverse effects. These theories have been tested in clinical trials in patients with advanced prostate cancer, as discussed in this Viewpoint.

The MammoSite^®breast brachytherapy applicator was designed to simplify the brachytherapy procedure and make it more accessible to patients who are suitable candidates for partial-breast irradiation (PBI). Dickler highlights the advantages of this technique such as low rates of serious complications and favorable cosmetic outcome and also summarizes ongoing trials that should provide a definitive answer regarding the benefits of PBI.

Carney's triad is a syndrome consisting of three rare neoplasms: gastric leiomyosarcoma, extra-adrenal paraganglioma and pulmonary chondroma. The article by Kächele et al. describes the case of a young woman who presented with a gastrointestinal stromal tumor and metastatic epicardial paraganglioma. The patient underwent an extended hemigastrectomy and cardiac surgery and remained free of recurrent disease during the follow-up period. This is the first report of an epicardial paraganglioma within a Carney's triad and the authors discuss the diagnostic workup and management of patients with Carney's syndrome.

Combining cytotoxic drugs with radiation is aimed at improving survival without compromising quality of life. While the current trend in treating epithelial tumors favors concurrent chemoradiation, future regimens should exploit spatial cooperation and temporal modulation mechanisms to optimize the balance between treatment risks and benefits. The authors of this review propose that effective exploration of novel strategies will require a rigorous scientific and mechanistic framework to best identify and test exploitable mechanisms of drug-radiation interaction.

In the first review of this two-part series, Seiwert and co-authors described the rationale for the use of concurrent chemoradiotherapy for treating malignancies. Here the chemoradiotherapy platforms used for the treatment of head and neck cancer are described and the integration of novel agents such as EGFR inhibitors and antiangiogenic drugs into treatment platforms alongside multiagent-based regimens are reviewed. The authors provide guidance for clinicians based on current clinical trial evidence and suggestions for choosing the most appropriate treatment platform.

Schneider and Sledge discuss the mechanisms of resistance associated with anti-angiogenic agents and the problems associated with defining which groups of patients might benefit from this class of therapy. This review highlights the rationale for targeting VEGF and how the combination of anti-angiogenic drugs with other biologic agents is also being explored in clinical trials, in an attempt to improve efficacy and to overcome resistance seen with the initially studied anti-angiogenic drugs.

The authors of this Viewpoint discuss the protective activity of fenretinide on second breast cancer as a surrogate marker of primary prevention and the possibility of using this agent in young women bearing germlineBRCA-1 and BRCA-2mutations.

In this Viewpoint the potential implications of improved understanding of the metastatic cascade in cancer patients are discussed. The detection of disseminated tumor cells before the onset of overt metastasis could improve stratification of patients who are in need of early systemic anti-cancer therapy; monitor the efficacy of such therapy; help to identify therapeutic targets; and assist in selection of cancer patients who are candidates for targeted therapies.

Individuals with recessive mutations in the mismatch repair geneMSH6 are at an increased risk of developing primary and secondary malignancies. In this article, Scott et al. describe the case of a young girl with constitutional biallelic MSH6 mutations who had developed colonic carcinomas, medulloblastoma and acute myeloid leukemia. The patient underwent allogeneic bone marrow transplantation and panproctocolectomy and was treated with chemotherapy. This report broadens the tumor spectrum associated with biallelic MSH6mutations and discusses the differential diagnosis and implications for treatment in individuals with such mutations.

Concurrent chemoradiotherapy is a highly efficacious locoregional treatment option for solid tumors. The rationale for the use of concurrent chemoradiotherapy for treating malignancies, and the molecular basis for combining classic cytotoxic agents and novel targeted therapies agents with radiotherapy are discussed. This article is part one of two articles. In the subsequent article, the general principles outlined here will be applied to head and neck cancer, where the impact of concurrent chemoradiotherapy is particularly evident.

Health care statistics demonstrate a striking disparity in treatment selection, access, and outcomes between the African-American community and the general population. The role of race and ethnicity in lung cancer etiology is unclear but genetic, cultural and socio-economic factors, in addition to differences in tobacco use and exposure contribute to this disparity. This review summarizes the existing body of knowledge regarding lung carcinoma in African Americans, and identifies promising areas for future investigation and intervention.