Reviews & Analysis

The combination of dyspnea, exercise limitation and muscle weakness is known as cancer fatigue syndrome. Dyspnea is an important symptom in patients with cancer and also in patients with chronic heart failure. The authors of this Viewpoint hypothesize that cancer fatigue syndrome represents clinically non-overt heart failure, and postulate that cardiac-like symptoms in cancer develop in a similar manner to symptoms of chronic heart failure.

The treatment options for patients with chemoresistant diffuse large B-cell lymphoma are limited. Fenske et al. describe the case of a 41-year-old man with chemorefractory lymphoma, who was treated with yttrium-90 microsphere embolization of his hepatic tumors. The patient's lymphoma progressed and he died, but there was no evidence of recurrence in the liver. The authors discuss yttrium-90 microsphere embolization for patients who have chemoresistant lymphoma with involvement of the liver.

Cardiovascular disease in patients with cancer and cardiac complications of cancer therapy is an increasing clinical problem. Optimum management of cardiovascular disease can allow patients with cancer to successfully receive cancer therapies and it can reduce morbidity and mortality caused by cardiovascular disease in cancer survivors. The authors of this review discuss management strategies for cardiovascular disease in patients with cancer, focusing on the prevention and treatment of congestive heart failure and myocardial infarction.

Five adjuvant breast cancer trials have clearly demonstrated the benefit of trastuzumab in reducing the recurrence rate and mortality in patients with aggressive HER2-positive disease. The controversies and challenges relating to the use of trastuzumab in the adjuvant setting, such as the optimal timing and duration, its use with taxanes and radiotherapy, its role in small node-negative tumors and cost-effectiveness are discussed.

Testicular germ-cell cancer is the most common solid malignancy affecting males in puberty and adulthood. Ponti et al. report the case of a 45-year-old man who was initially misdiagnosed with stage I seminoma, developed brain metastases and finally died. Pathology review showed large B-cell lymphoma in the primary tumor. The authors underline the need for accurate histology review in testicular tumors with unusual clinical features.

The current method for assessing response to therapy of glial tumors is based on the Macdonald et al. criteria; however, these criteria are ambiguous in key features such as the appropriate threshold for lesion size and the actual methods for applying the stated criteria. The authors of this Review identify the strengths and shortcomings of the current approach and also discuss technological advances in both drug therapy and imaging that necessitate reassessment of the Macdonald et al. criteria.

Technologies such as mass spectrometry, and protein and DNA arrays, have enabled simultaneous examination of thousands of proteins and genes, giving opportunities to identify distinguishing signatures for cancer diagnosis and classification and prediction of therapeutic response. The authors provide an overview of how the current cancer biomarkers were discovered and their associated limitations, discuss the utilization of these emerging technologies, and review their potential to revolutionize biomarker discovery.

The value of sentinel-node biopsy for the management of localized primary melanoma has been questioned. In this Viewpoint, the authors discuss the data that support the routine use of sentinel-node biopsy, and assert why this technique should be considered the standard approach for staging patients with clinically localized, intermediate-thickness melanoma.

Our understanding of the biology of Hodgkin's lymphoma has improved, in particular the genetic and phenotypic characteristics of malignant cells and the signaling pathways involved in the pathogenesis of this disease. While newer regimens have improved the cure rates of patients with Hodgkin's lymphoma, some are associated with severe acute and long-term toxicities. This comprehensive Review discusses combined modality regimens for treating early-stage disease, approaches used for treating advanced disease and other novel regimens.

The prognosis for patients with advanced melanoma and CNS metastases is poor. Hodi et al. report the case of a 63-year-old female who was diagnosed with metastatic melanoma from an unknown primary tumor. The authors discuss the use of the human monoclonal antibody against CTLA-4, ipilimumab, in patients with metastatic melanoma.

In epithelial ovarian cancer, gene-expression profiling has been used to provide prognostic information, to predict response to first-line platinum-based chemotherapy, and to discriminate between different histologic subtypes. The authors of this Review summarize the contributions of gene-expression profiling to the diagnosis and management of epithelial ovarian cancer and discuss ways in which this technique could become a useful tool in clinical management.

Over 80% of men with advanced prostate cancer respond to standard treatment with continuous androgen deprivation therapy. Most of these patients, however, go on to develop androgen resistance and disease progression. The authors of this Viewpoint propose that intermittent androgen deprivation should be the standard therapy in advanced prostate cancer.

Our understanding of the pathogenesis of tobacco-related lung carcinogenesis is improving but the molecular mechanisms of neoplastic transformation in never-smokers have not yet been elucidated. Mountzios et al. describe the best characterized signaling pathways that are implicated in the transduction of proliferative signals, and discuss the differences in the molecular characteristics of smokers and never-smokers.

Over half of all newly-diagnosed diffuse large B-cell lymphoma patients can be cured with first line treatment based on the combination of rituximab with anthracycline-based chemotherapy regimens. The authors of this Viewpoint discuss the use of high-dose therapy and autologous hematopoietic stem cell support in patients with DLBCL who have relapsed or are refractory to first line treatment.

Mammalian target of rapamycin (mTOR) is an important and clinically relevant therapeutic target. Temsirolimus has significantly improved overall survival rates in patients with advanced renal cell carcinoma, thereby validating the importance of mTOR in the natural history of this disease. This Review discusses the clinical development of temsirolimus, its novel mechanism of action, and the investigational strategies for targeting mTOR in other tumor types.

Estrogen-deprivation strategies with aromatase inhibitors are superior to tamoxifen in the adjuvant, neoadjuvant and advanced breast-cancer settings in postmenopausal patients. Short-term hormonal resistance especially in the HER2-positive patient population, however, is a significant issue with these endocrine agents. The authors discuss the progress made in our understanding of resistance to endocrine therapy, and provide insights regarding the management of patients with hormone receptor-positive/HER2-positive advanced breast cancer.

There are few treatment options for patients with metastatic HER2-positive breast cancer who are unresponsive to trastuzumab. The combination of lapatinib and capecitabine significantly prolongs time to disease progression in women previously treated with chemotherapy and trastuzumab for HER2-positive advanced disease. The rationale for using this combination and the promising activity of lapatinib in early trials of inflammatory breast cancer is highlighted.

It is unlikely that tumors are entirely dependent on only one abnormally activated signaling pathway and, consequently, treatment with an agent interfering with a single target may be insufficient. This Review discusses the experimental and early-stage clinical evidence to support the relevance of EGFR-dependent and VEGF-dependent pathways, their functional links and the implications of acquired resistance to targeted therapies.

There is a paucity of phase III data comparing chemoradiation with radiation alone for treating invasive bladder cancer; however, an ongoing Australian trial is attempting to address this lack of data. Strategies that combine systemic chemotherapy and radiotherapy have been explored and have yielded better local control than either modality alone. The role of systemic chemotherapy and the controversies surrounding the use of radical surgery versus chemoradiation are discussed.

The tumor suppressor syndrome neurofibromatosis type 2 (NF2) is transmitted in an autosomal dominant fashion. Plotkin et al. report the case of a 48-year-old man who was diagnosed with progressive NF2-related vestibular schwannomas and received erlotinib therapy, which resulted in improved audiologic and radiographic responses. The authors discuss the potential effectiveness of targeted therapies for progressive vestibular schwannoma in NF2 patients.