CD44 is prognostic for overall survival in the NCI randomized trial on breast conservation with 25 year follow-up.

CD44 is a transmembrane glycoprotein involved in numerous cellular functions, including cell adhesion and extracellular matrix interactions. It is known to be functionally diverse, with alternative splice variants increasingly implicated as a marker for tumor-initiating stem cells associated with poor prognosis. Here, we evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue specimens from patients treated on the National Cancer Institute 79-C-0111 randomized trial of breast conservation versus mastectomy between 1979 and 1987 were collected, and immunohistochemistry was performed using the standard isoform of CD44. Specimens were correlated with patient characteristics and outcomes. Survival analysis was performed using the log rank test. Fifty-one patients had evaluable tumor sections and available long-term clinical follow up data at a median follow up of 25.7 years. Significant predictors of OS were tumor size (median OFS 25.4 years for ≤2 cm vs. 7.5 years for >2 cm, p = 0.001), nodal status (median OS 17.2 years for node-negative patients vs. 6.7 years for node positive patients, p = 0.017), and CD44 expression (median OS 18.9 years for CD44 positive patients vs. 8.6 years for CD44 negative patients, p = 0.049). There was a trend toward increased PFS for patients with CD44 positive tumors (median PFS 17.9 vs. 4.3 years, p = 0.17), but this did not reach statistical significance. These findings illustrate the potential utility of CD44 as a prognostic marker for early stage breast cancer. Subgroup analysis in patients with lymph node involvement revealed CD44 positivity to be most strongly associated with increased survival, suggesting a potential role of CD44 in decision making for axillary management. As there is increasing interest in CD44 as a therapeutic target in ongoing clinical trials, the results of this study suggest additional investigation regarding the role CD44 in breast cancer is warranted.

Pulmonary function following total body irradiation (with or without lung shielding) and allogeneic peripheral blood stem cell transplant.

Our purpose was to determine if total body irradiation (TBI) with lung dose reduction protects against subsequent radiation-induced deterioration in pulmonary function. Between July 1997 and August 2004, 181 consecutive patients with hematologic malignancies received fractionated TBI before allogeneic peripheral blood stem cell transplant. The first 89 patients were treated to a total dose of 13.6 Gy. Thereafter, total body dose was decreased to 12 Gy with lung dose reduction to 9 or 6 Gy. All patients underwent pulmonary function test evaluation before treatment, 90 days post-treatment, then annually. Median follow-up was 24.0 months. Eighty-nine patients were treated with lung shielding, and 92 without. At 1-year post transplant, there was a small but significant difference in lung volume measurements between patients with lung shielding and those without. This was not observed at the 2-year time point. When stratified by good (>100% predicted) or poor (