Evaluation of Changes in Circulating Cell-Free DNA as an Early Predictor of Response to Chemoradiation in Rectal Cancer-A Pilot Study.

Background and Objectives: The objective of this study was to investigate quantitative changes in cell-free DNA (cfDNA) found in the bloodstream of patients with locally advanced rectal cancer who received neoadjuvant long-course chemoradiation, assuming a change in DNA fragments release during therapeutic stress. Materials and Methods: This was a prospective observational study that involved 49 patients who had three distinct pathologies requiring neoadjuvant chemoradiation: 18 patients with breast cancer, 18 patients with cervical cancer, and 13 patients with rectal cancer. Both breast cancer and cervical cancer patients were used as a control groups. Breast cancer patients were used as a control group as irradiation targeted healthy tissue after the tumor resection (R0), while cervical cancer patients were used as a control group to evaluate the effect of chemoradiation regarding cfDNA in a different setting (squamous cell carcinomas) and a different tumor burden. Rectal cancer patients were the study group, and were prospectively evaluated for a correlation between fragmentation of cfDNA and late response to chemoradiation. Blood samples were collected before the initiation of treatment and after the fifth radiation dose delivery. cfDNA was quantified in peripheral blood and compared with the patients' clinicopathological characteristics and tumor volume. Conclusion: Thirteen patients with locally advanced rectal cancer (T3/T4/N+/M0) were included in the study, and all of them had their samples analyzed. Eight were male (61.54%) and five were female (38.46%), with an average age of 70.85 years. Most of the patients had cT3 (53.85%) or cT4 (46.15%) tumors, and 92.31% had positive lymph nodes (N2-3). Of the thirteen patients, only six underwent surgery, and one of them achieved a pathological complete response (pCR). The mean size of the tumor was 122.60 mm3 [35.33-662.60 mm3]. No significant correlation was found between cfDNA, tumor volume, and tumor regression grade. cfDNA does not seem to predict response to neoadjuvant chemoradiotherapy and it is not correlated to tumor volume or tumor regression grade.

[Triple-negative breast cancer--towards a new entity]. / Cancerul mamar triplu negativ--spre o noua entitate.

UNLABELLED: Breast cancer is considered today as a heterogeneous group of diseases, with a wide spectrum of clinical, pathologic and molecular features. A new classification of breast carcinomas, based on gene expression profiles technologies (cDNA microarray), shows impact on the diagnosis and prognostic classification of tumors, prediction of response of individual patients to specific chemotherapeutic regimens, and identification of novel tumor targets. AIM: To identify the proportion of basal-like ("triple-negative") tumors in patients treated for breast carcinoma. OBJECTIVES: To evaluate the impact of molecular subtyping on treatment response, disease-free survival and overall survival of patients, and to establish and correlate particular biologic, clinical and diagnostic features of these cancers. METHODS: 96 patients with breast cancer, aged 28-78 years, were retrospectively selected using specific criteria from cases treated between 2001 and 2007 in the Oncology Department of the "Sf. Spiridon" Hospital Iasi. Tumors were divided into molecular subtypes using immunohistochemistry data. RESULTS: The most frequent pathology was ductal carcinoma (77 patients, 80.2%), and most tumors were intermediately or poorly differentiated (G2 43 patients, 44.8%; G3 37 patients, 38.5%) The proportion of basal-like tumors in the population sample analyzed was 15.62% (15 patients). Histological type (p=0.85), pTNM stage (p=0.618), and tumor differentiation grading (p=0.54) did not correlate with molecular subtype. Patients with basal-like tumors had lower time-to-progression (mean 31.2 months, 95%CI 18.5-43.8, p=0.005), disease free survival (mean 24.46 months, 95%CI 12.6-36.3, p=0.016), and overall survival (mean 39.26 months, 95%CI 26.7-51.7, p=0.023). CONCLUSION: We have demonstrated, using the simple commonly available immunohistochemical markers ER, PR and HER2/neu, that patients with triple negative breast cancers have relatively poor prognosis, with significantly shorter survival and a poorer response to standard treatment strategies.