Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study.

BACKGROUND: Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. METHODS: Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade. RESULTS: Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions. CONCLUSIONS: This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].

IGG practice guidelines on germ cell tumor in adult male patients.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30-40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.

Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer.

PURPOSE: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. METHODS AND MATERIALS: Treatment consisted of a mobilizing course of epirubicin 150 mg/m2, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m2 (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m2, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m2 (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients were treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. RESULTS: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. CONCLUSION: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.