February 2006

Editors:
Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

MammoSite excision volume as a predictor for residual disease

The MammoSite catheter is a bracytherapy device used for accelerated partial breast irradiation. It is available as two spherically shaped balloons meant to fill 70-cc and 120-cc cavity volumes. The authors conducted a study to define the relationship between these excision volumes and the likelihood of microscopically detectable, residual disease based on tumor size, margin status, patient age, and histology. The study database was composed of 531 patients with stages 0, I, and II breast carcinoma (using American Joint Committee on Cancer staging criteria) who received breast-conserving therapy and underwent surgical re-excision. Patients in the database were stratified based on the volume of their initial excision: less than or equal to 70 cc versus greater than 70 cc, and less than or equal to 120 cc versus greater than 120 cc. The authors found that surgical margin size was a strong predictor of residual disease for patients with smaller excision volumes (P=0.0014) and patients with larger excision volumes (P=0.0003). Histology (extensive intraductal component [EIC] or pure ductal carcinoma in situ [DCIS]) was also a strong predictor of residual disease. Tumor size was significant only for the larger volume group (P=0.029). On multivariate analysis, only histology and initial margin status were significant correlates with residual disease. The adjusted odds ratio for residual disease with pure DCIS was 0.79, and the adjusted odds ratio for invasive ductal or lobular carcinoma (IDC/ILC) without EIC was 0.44 relative to IDC/ILC with EIC (P=0.008). The adjusted odds ratio for residual disease with a positive initial margin versus a negative initial margin was 2.65 (P<0.0001). The authors concluded that for excisions amenable to use of the MammoSite catheter, a margin of greater than or equal to 1.0 mm appeared to afford at most a 35 percent risk of microscopically detectable residual tumor. Evidence of EIC on excision of IDC/ILC connoted a significantly higher risk. Age did not appear to be predictive for residual disease.

Kaufman SA, DiPetrillo TA, Ruthazer R, et al. MammoSite excision volume as a predictor for residual disease. Cancer. 2005;104:906-912.

Reprints: Dr. Seth A. Kaufman, Dept. of Radiation Oncology, Tufts-New England Medical Center, Box 359, Boston, MA 02111; skaufman1@tufts-nemc.org

Analysis of presumptive prognostic markers among oligodendrogliomas

Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene methylguanine methyltransferase (MGMT) is diminished in 80 percent of oligodendroglial tumors and represents a possible mechanism for this therapeutic sensitivity. However, the authors of this study questioned the relevance of genetic testing and measuring MGMT levels in tumors that were diagnostic of oligodendroglioma. They performed a retrospective analysis of 1p, 19q, 9p21, TP53, and MGMT status in 46 patients with oligodendrogliomas to address any relationships that may exist between these markers with regard to progression-free survival and total survival. Methodologies included comparative genomic hybridization; loss of heterozygosity (LOH) on 1p, 19q, and 9p21; TP53 mutational analysis; and immunohistochemistry for MGMT. The authors found that survival among patients with light microscopically diagnosed oligodendroglial tumors demonstrating LOH of 1p and 19q trended toward statistical significance (P=0.102 and P=0.058, respectively). 9p21 LOH was significant as a predictor of progression-free survival only among anaplastic oligodendrogliomas in this cohort (P=0.033). TP53 mutation was found to be significantly predictive of a shorter survival (P=0.027) among all patients and exhibited a strong trend toward a shorter progression-free survival (P=0.060). Low-level MGMT labeling index (less than 20 percent) was noted in 86 percent of all oligodendroglial tumors. MGMT labeling index was not found to correlate with an improved progression-free survival or total survival in this cohort, recognizing that median survival was not reached after a median followup of 104 months. The authors concluded that 9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas.

McLendon RE, Herndon JE, West B, et al. Survival analysis of presumptive prognostic markers among oligodendrogliomas. Cancer. 2005;104:1693-1699.

Reprints: Dr. Roger E. McLendon, Dept. of Pathology, Duke University Medical Center, P.O. Box 3712, Durham, NC 27710; roger.mclendon@duke.edu

Multifocal and multicentric breast cancer: Does each focus matter?

The authors conducted a study to see if multiple tumors in the breast are associated with increased nodal involvement when compared with similar staged unifocal disease. Their study compared two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer. The authors examined the histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995. Tumors were assessed using the largest tumor focus diameter and the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against nodal positivity. The authors found that 94 (11.1 percent) of 848 women had multifocal breast cancer, and of these, 49 women (52.1 percent) had axillary node involvement, compared with 37.5 percent with unifocal breast cancer (P=0.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Using this method to stage cancers, rather than largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas. The authors concluded that the tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman’s disease. This may deny patients the opportunity of adjuvant therapies if doctors ignore the contribution of the smaller foci to the incidence of node positivity and survival.

Coombs NJ, Boyages J. Multifocal and multicentric breast cancer: Does each focus matter? J Clin Oncol. 2005;23:7497-7502.

Reprints: John Boyages, New South Wales Breast Cancer Institute, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; johnb@bci.org.au