Reviews & Analysis

Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. Currently, surgery remains the treatment of choice for HCC; however, due to underlying liver disease only a minority of those affected are candidates for resection, and access to transplantation is limited by organ availability. The authors of this review discuss when liver resection, nonsurgical HCC treatment and management before liver transplantation should be considered, and the applications of nonsystemic therapies.

There are a number of factors that make cancer screening more difficult in the lungs than in other organs. These factors include the characteristics of the patient group being screened, the heterogeneous nature of lung cancer and issues with the screening process itself, as discussed in this Viewpoint.

The evidence for use of spiral CT for lung cancer screening and the results and implications of the International Early Lung Cancer Action Program study are discussed in this Viewpoint.

This Viewpoint compares targeted intraoperative radiotherapy with other forms of partial breast irradiation. Advantages of targeted intraoperative radiotherapy include reduced risk of the target area being untreated, the potential to add external-beam whole-breast radiotherapy, cost-effectiveness of this technique and relatively straightforward technical requirements.

This Viewpoint compares external-beam-based partial breast irradiation with other forms of partial breast irradiation. With appropriate patient selection, delivery of partial breast irradiation through an external-beam approach presents many advantages, including patient acceptability, ease of use and cost effectiveness. Silvia Formenti discusses the relative merits of prone and supine patient positioning during external-beam radiotherapy and the important challenges that remain.

This Viewpoint compares MammoSite^® brachytherapy with other forms of partial breast irradiation. Although very few reports on clinical efficacy have been published, indications so far are that the MammoSite^®catheter is technically simple, adequately spares normal tissues, and is associated with a favorable cosmetic outcome and toxicity profile. The choice of the optimal irradiation method remains complex and requires input from both treating physicians and their patients.

Cervical cancer is one of the most frequent malignancies diagnosed during pregnancy. Karam et al. report the case of a 28-year-old woman who was diagnosed with poorly-differentiated stage IB2 squamous-cell cervical carcinoma at 23 weeks of gestation. The patient received neoadjuvant cisplatin, underwent radical cesarean hysterectomy and after delivery commenced pelvic radiation therapy with cisplatin chemosensitization. The authors discuss the treatment and management options for women diagnosed with cervical carcinoma during pregnancy and review the reported experience with the use of chemotherapy in such cases.

Malignant pleural mesothelioma (MPM) is a common primary tumor of the pleura. Current therapeutic regimens that involve surgery, chemotherapy and radiotherapy have offered marginal clinical benefits. Histological subtype, lymph-node involvement, resection margins and invasion beyond the pleura are significant factors that dictate survival. This review discusses the multimodality approach, which is considered the cornerstone of treatment of MPM, although the authors emphasize that the exact combination of treatment options for this disease have yet to be defined.

Brain tumors are currently diagnosed on the basis of their histology, but recent findings indicate that in some cases response to conventional therapy correlates with genetic characteristics rather than histopathology. An understanding of the molecular mechanisms that underlie the malignant phenotype of gliomas also provides the possibility of rational design of molecular targeted therapies, as discussed in this review.

Fertility preservation is an important component of cervical cancer treatment, and recently radical surgical procedures have been used in favor of more conservative techniques in an effort to decrease morbidity and preserve fertility without compromising overall survival. The authors of this Review suggest radical vaginal trachelectomy is a safe and feasible procedure in women wishing to preserve fertility, and they review the preoperative considerations, surgical complications and the risk factors associated with this technique.

This Viewpoint compares multicatheter brachytherapy with other forms of partial breast irradiation. As the forerunner of other ABPI techniques, interstitial brachytherapy has to its credit the best intermediate-term to long-term oncological and cosmetic results, and to its discredit some of the highest recurrence and complication rates. Enhancements to quality assurance and patient selection criteria could hold the key to best practice.

The authors of this Viewpoint argue there are no facile solutions to replace the painstaking, empirical effort required to identify the targets within 'addicted' tumors. Redundant pathways and our incomplete understanding of drug targets cast doubt on biomarker evidence unless reinforced by biological observations. Further integration of academia, industry and the regulatory organizations is required.

Localized rectal adenocarcinoma responds well to 5-fluorouracil/radiation-based therapy. Willett et al. present the case of a 55-year-old woman who was diagnosed with extensive and locally invasive carcinoma of the rectum and received bevacizumab in combination with chemoradiotherapy. Upon completion of neoadjuvant therapy, the patient underwent abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy. The authors discuss the complete response seen in this patient and insights into the application and clinical management of using anti-VEGF therapy with chemoradiation.

The methyl binding domain family of proteins have a significant role in controlling gene expressionin vivo, and have been linked to multiple and diverse functions in tumorigenesis. DNA hypermethylation is a well-recognized mechanism underlying gene silencing events in both tumorigenesis and drug resistance. The authors of this review shed light on the mechanisms of this protein family and explain why it is likely that these proteins will be important novel therapeutic targets in the future.

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.