Telomere-Specific Reverse Transcriptase (hTERT) and Cell-free RNA in Plasma as Predictors of Pathologic Tumor Response in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy

PURPOSE: To investigate whether the plasma levels of cell-free RNA (cfRNA) and telomere-specific reverse transcriptase mRNA (hTERT) are associated with tumor response in rectal cancer patients who received preoperative chemoradiotherapy (pCRT). METHODS: Patients who underwent pCRT for rectal cancer and for whom baseline and paired post-pCRT blood samples were available were studied. On the basis of tumor regression score, patients were classified as having response or having no response. Clinical variables and plasma levels of cfRNA and hTERT before and after the pCRT were evaluated. The association between each predictor and tumor response was assessed by univariate and multivariate analyses. RESULTS: Of 98 eligible patients, 45 were determined to respond to therapy, and 53 did not respond to therapy. In univariate analysis, gender (P = 0.040), baseline levels of cfRNA (P = 0.026), post-pCRT levels of both hTERT and cfRNA (P < 0.0001 and P = 0.001, respectively), and the difference between the post- and pre-pCRT levels of both hTERT and cfRNA (P = 0.009 and P = 0.001, respectively) were found to be significant predictors of tumor response. In multivariate analysis, using variables that were available before pCRT, cfRNA levels and gender independently predicted the tumor response, while in multivariate analysis, which used all of the variables available before the surgical procedure, the post-pCRT levels of cfRNA and the difference between the post- and pre-pCRT levels of cfRNA independently predicted tumor response. CONCLUSIONS: Plasma levels of cfRNA and hTERT are promising markers of tumor response to pCRT for rectal cancer

Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

n rectal cancer, a pathologic complete response (pCR) to pre-operative treatment is a favourable prognostic marker, but is reported in a minority of the patients. We aimed at identifying microRNA-related host genetic polymorphisms predictive of pCR. A panel of 114 microRNA-related tagging polymorphisms was selected and analyzed on 265 locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. Patients were stratified in two subgroups according to the radiotherapy dose (50.4Gy for 202 patients, 55.0Gy for 78 patients). Interactions among genetic and clinical-pathological variants were investigated by recursive partitioning analysis. Only polymorphisms with a consistent significant effect in the two subgroups of patients were selected as predictive markers of pCR. The results were validated by bootstrap analysis. SMAD3-rs744910, SMAD3-rs745103, and TRBP-rs6088619 were associated to an increased chance of pCR (p=0.0153, p=0.0471, p=0.0125). DROSHA-rs10719 and SMAD3-rs17228212 had an opposite detrimental effect on pathological tumour response (p=0.0274, p=0.0049). Recursive partitioning analysis highlighted that a longer interval time between the end of radiotherapy and surgery increases the chance of pCR in patients with a specific combination of SMAD3-rs744910 and TRBP-rs6088619 genotypes. This study demonstrated that microRNA-related host genetic polymorphisms can predict pCR to neo-adjuvant chemo-radiotherapy, and could be used to personalize the interval time between the end of radiotherapy and surgery

The JANUS camera onboard JUICE mission for Jupiter system optical imaging

JANUS (Jovis, Amorum ac Natorum Undique Scrutator) is the visible camera selected for the ESA JUICE mission to the Jupiter system. Resources constraints, S/C characteristics, mission design, environment and the great variability of observing conditions for several targets put stringent constraints on instrument architecture. In addition to the usual requirements for a planetary mission, the problem of mass and power consumption is particularly stringent due to the long-lasting cruising and operations at large distance from the Sun. JANUS design shall cope with a wide range of targets, from Jupiter atmosphere, to solid satellite surfaces, exosphere, rings, and lightning, all to be observed in several color and narrow-band filters. All targets shall be tracked during the mission and in some specific cases the DTM will be derived from stereo imaging. Mission design allows a quite long time range for observations in Jupiter system, with orbits around Jupiter and multiple fly-bys of satellites for 2.5 years, followed by about 6 months in orbit around Ganymede, at surface distances variable from 104 to few hundreds km. Our concept was based on a single optical channel, which was fine-tuned to cover all scientific objectives based on low to high-resolution imaging. A catoptric telescope with excellent optical quality is coupled with a rectangular detector, avoiding any scanning mechanism. In this paper the present JANUS design and its foreseen scientific capabilities are discussed

Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: Long-term analysis of 566 ypcr patients

Purpose: In the literature, a favorable prognosis was observed for complete pathologic response after preoperative therapy (ypCR) in patients with locally advanced rectal cancer. The aim of this study is to verify whether ypCR predicts a favorable outcome in a large series of patients. Methods and Materials: The Gastro-Intestinal Working Group of the Italian Association of Radiation Oncology collected clinical data for 566 patients with ypCR (ypT0N0) after neoadjuvant therapy. Eligibility criteria included locally advanced rectal cancer,with no evidence of metastases at the time of diagnosis, evidence of ypCR after preoperative radiotherapy chemotherapy (CT). Results: Median radiation dose was 50 Gy. A total of 527 patients (93%) received one of 12 different neoadjuvant CT schedules. Sphincter preservation, anteroposterior resection, and endoscopic surgery were performed in 73%, 22%, and 5% of patients, respectively. Adjuvant CT was administered to 22% of patients. Median follow-up was 46.4 months. Locoregional recurrence occurred in 7 patients (1.6%). Distant metastases occurred in 49 patients (8.9%). Overall, 5-year rates of disease-free survival, overall survival, and cancer-specific survival were 85%, 90%, and 94%, respectively. In multivariate analysis , only age and clinical stage statistically correlated with survival outcome. Adjuvant CT was still of borderline significance (worse for adjuvant CT). No relation was found between survival and neoadjuvant CT schedules. Conclusion: A ypCR after neoadjuvant therapy identified a favorable group of patients, even in this large series or 566 patients collected in 61 centers. Locoregional recurrence occurred only in 1.6% patients. (C) 2008 Elsevier Inc