Volume 7 Issue 4, April 2010

The results of a randomized, controlled trial investigating the neurocognitive effects of stereotactic radiosurgery (SRS), with or without whole-brain radiation therapy (WBRT), to treat brain metastases demonstrated a significant reduction in learning and memory, associated with the addition of WBRT to SRS. The results indicate that SRS monotherapy is an effective and safe initial management strategy for brain metastases.

The addition of zoledronic acid to aromatase inhibitors is associated with improved bone mineral density, but not with an effect on clinically-meaningful end points such as fractures. The oncology community should prioritize the design of trials evaluating more relevant end points, such as fragility fracture risk, for treatment-induced bone loss and critically assess the effects of such treatment on breast cancer survival.

The effect of PSA level on distant metastases and cause-specific mortality was assessed in a recent study, and showed a nadir PSA level 1.5 ng/ml within 2 years of radiotherapy treatment predicts distant metastases and death from prostate cancer.

Patients who undergo hepatic surgery for initially resectable liver metastases from colorectal cancer have a 70% risk of relapse. A recent phase III randomized trial has failed to demonstrate an improvement in disease-free survival with the addition of irinotecan to 5-fluorouracil and folinic acid as adjuvant treatment for patients with radically resected colorectal cancer with liver metastases.

Dose-dense administration of paclitaxel as well as intraperitoneal administration of platinum and paclitaxel as first-line treatments provide similar advantages compared with standard treatment in advanced ovarian cancer. Both approaches, however, need to be confirmed by additional studies. A low dose of pegylated liposomal doxorubicin combined with carboplatin is superior to standard paclitaxel and carboplatin in relapsed platinum-sensitive ovarian cancer.

EGFR inhibitors provide benefit in patients with advanced and metastatic head and neck squamous cell carcinoma (HNSCC). Mass spectrometry profiling has been used to predict outcome in patients with HNSCC after EGFR inhibitor treatment, and may enable prior identification of patients most likely to benefit from these therapies. However, further validation in prospective studies is needed.

Mutations in the mismatch repair (MMR) genes are associated with an increased risk of developing colorectal cancer (CRC). In this Review, the authors outline the MMR system and describe how defective MMR impacts on the management of CRC. The authors also discuss how targeting these mutations can be exploited in the development of novel therapeutic strategies.

Mammalian target of rapamycin (mTOR) has a key role in several pathways that are involved in cell growth and cancer. In this Review, Dr. Dancey outlines the mechanisms of action and performance of current mTOR inhibitors in clinical trials. Second-generation inhibitors are also discussed along with strategies that should be used to improve outcomes achieved with mTOR inhibitors.

Painful bone metastases can be treated with radiotherapy, and single-fraction radiotherapy with 1 × 8 Gy has been shown to be as effective for pain relief as multi-fraction regimens. The authors discuss why single-fraction radiotherapy is considered the standard regimen for uncomplicated painful bone metastases without pathological fractures or spinal cord compression, and highlight the reasons why long-course multi-fraction radiotherapy should be reserved for patients with a relatively favorable survival prognosis.

Surgery of esophageal cancer is associated with a poor prognosis, yet there is no international consensus on the optimal management of operable esophageal cancer. The authors of this Review discuss the role of perioperative chemotherapy and definitive chemoradiation, and the associated survival benefits.