Kennedy's GBM treatment

Regardless of your political persuasion, Ted Kennedy was a force in the Senate, and shaped much of the current dialogue on health care reform (in addition to many other issues over his long political career). As his treatment involved surgery at Duke and proton therapy in Boston, it may be of interest to read media reports of his treatment course:

Link to CNN article

Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures

Very interesting article on the use of medical imaging and the resulting dose in a broad population sample in this weeks NEJM.

Link:
Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures: "The use of medical imaging procedures has been increasing, and this study estimated the exposure of U.S. patients to low-dose ionizing radiation from these procedures. The exposure was substantial, largely because of radiation from computed tomography and nuclear imaging. The highest average effective dose was attributable to myocardial perfusion imaging, and most imaging occurred in outpatient settings. These data indicate that the use of imaging can result in high radiation doses. "

Antioxidants and Cancer: More Caution

This week's nature has a very interesting article on a potential pro-survival effect of antioxidants on metastatic cells. This stems from the observation that cells that loose attachment to the extracellular matrix (ECM), have increased levels of reactive oxygen species (ROS) intracellularly, leading to a reduced atp levels. In this model, these defects were reversed by the application of antioxidants (NAC or a vitamin E derivative).

Of course we have been telling patients for years not to take large amounts of antioxidants during radiation therapy due to the potential reversal of the oxygen dependent indirect effect of RT. This however is a much broader cautionary tale, albiet without any direct human clinical data at this time...

Link:

nature: Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment

Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer

Banner day for oncology in this weeks NEJM:

The BIG 1-98 trial comparing different hormonal manipulations for the adjuvant treatment of postmenopausal women have finally reported on the "switching" arms of the trial. This trial has previously reported that the tamoxifen only arm was inferior to the letrozole arm, however there were those that believed that a switch between tamoxifen and letrozole would be beneficial. That has not been born out in these results, with the tamoxifen early arm demonstrating more early recurrences than the other arms.

Link:

Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer: "This study of adjuvant hormonal therapy in postmenopausal women with hormone-receptor-positive early breast cancer showed that disease-free survival was similar after 5 years of treatment with letrozole alone, 2 years of treatment with letrozole followed by 3 years with tamoxifen, or 2 years of treatment with tamoxifen followed by 3 years with letrozole. Five years of letrozole monotherapy may be superior to 5 years of tamoxifen monotherapy. "

Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer

The NEJM this week has an article directly relevant to patients receiving long term androgen deprivation with radiation therapy for high risk prostate cancer. In this phase III trial, patients undergoing androgen deprivation were randomized to receive denosumab, a monoclonal antibody targeting the NFKB ligand. The intervention resulted in improved bone density, and perhaps more importantly, resulted in decreased vertebral fractures, all at no significant observed toxicities.

This joins a number of randomized trials conducted by Dr. Smith and others on similar agents (see table below). What remains to be seen is what the best intervention is, both in terms of efficacy and cost.



Link:

Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer

Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer

NEJM has two interesting articles on EGFR recepter mutations and response to targeted treatments. The first of these demonstrates the incidence of EGRF mutations in the NSCLC population, and highlights the known associated demographic characteristics: non or light female smokers with adenocarcinoma. The study also demonstrates increased benefit to erolotinib, a TKI targeting the receptor.

Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer

Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma

This weeks NEJM has a quite striking phase III trial comparing a gefitinib to a carbo-taxol in a carefully selected cohort: non or light smokers from east asia with adenocarcinoma of the lung. This subset has been previously described as having an excellent response to treatment, but the very positive results of this trial prove a very significant benefit to disease free survival, and also demonstrate that the benefit in this subpopulation is related to EGFR mutation status.

Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma

Weight Lifting in Women with Breast-Cancer-Related Lymphedema

From the NEJM this week: An interesting randomized trial looking at lymphedema after breast cancer treatment, and challenging some of the paradigms of prevention.

Weight Lifting in Women with Breast-Cancer-Related Lymphedema: "Weight lifting has generally been discouraged for women with breast-cancer-related lymphedema because of concern that it might worsen the lymphedema. In this randomized trial involving breast-cancer survivors with lymphedema, women undergoing a 1-year weight-lifting program were no more likely than controls to have increased arm swelling, had greater improvement in the severity of lymphedema symptoms and strength, and had a lower incidence of confirmed exacerbations of lymphedema."

Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer

From the NEJM this week: One of the first studies showing that micromets are clinically significant (in a large retrospective series).

Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer: "This study involving women with early-stage breast cancer showed an association between the presence of isolated tumor cells or micrometastases in sentinel or axillary lymph nodes and the 5-year rate of disease-free survival. Women with such findings in these lymph nodes who received systemic adjuvant therapy had an improved outcome.

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