In this study we investigated the characteristics of a commercial ion chamber array and its performance in the verification of radiotherapy plans. The device was the 2D Array Seven29 model (PTW, Freiburg, Germany). This is a two-dimensional detector array with 729 ionization chambers uniformly arranged in a 27 x 27 matrix with an active area of 27 x 27 cm(2). The detector short-, medium- and long-term reproducibility have been tested through an extensive set of repeated measurements. Short-term reproducibility was well within 0.2%. Medium- and long-term reproducibility were within 1%, including set-up reproducibility errors and linac output fluctuations. Dose linearity was also assessed. The system response to dose was verified to be linear within the range 2-500 MU. Output factors matched very well pinpoint chamber measurements performed in the same experimental conditions with a maximum local percentage difference of 0.4%. Furthermore, the 2D Array sensitivity to millimetric collimator positional changes and to perturbation effect of irradiated area was tested. The comparison with ion chamber data carried out in water was very satisfying. Finally, measurements of wedge-modulated fields and IMRT beam sequence matched very well ion chamber dose profiles acquired in a water tank. The extensive tests performed in this investigation show that the 2D Array Seven29 is a reliable and accurate dosimeter and that it could be a useful tool for the quality assurance and the verification of radiotherapy plans.

A causal link between Human Papillomavirus (HPV) and breast cancer (BC) remains controversial. In spite of this, the observation that HPV DNA is over-represented in the Triple Negative (TN) BC has been reported. Here we remark the high prevalence of HPV DNA (44.4%) in aggressive BC subtypes (TN and HER2+) in a population of 273 Italian women and we convey the presence of HPV DNA in the epithelial and stromal compartments by in situ hybridization. As previously reported, we also found that serum derived-extracellular vesicles (EVs) from BC affected patients contain HPV DNA. Interestingly, in one TNBC patient, the same HPV DNA type was detected in the serum-derived EVs, cervical and BC tissue samples. Then, we report that HPV DNA can be transferred by EVs to recipient BC stromal cells that show an activated phenotype (e.g., CD44, IL6 expression) and an enhanced capability to sustain mammospheres (MS) formation. These data suggest that HPV DNA vehiculated by EVs is a potential trigger for BC niche aggressiveness.

We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long‐term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973–2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose–response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04–1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01–1.77), but we did not find signs of a dose–response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99–4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14–9.43). A competing risks analysis revealed that the clinical impact of radiation‐induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose–response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

No abstract

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as “synthetic torpor” in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Here we show the preliminary results from an experiment in rats exposed to ionizing radiation in normothermic conditions or synthetic torpor. Animals were irradiated with 3 Gy X-rays and organs were collected 4 h after exposure. Histological analysis of liver and testicle showed a reduced toxicity in animals irradiated in torpor compared to controls irradiated at normal temperature and metabolic activity. The expression of ataxia telangiectasia mutated (ATM) in the liver was significantly downregulated in the group of animal in synthetic torpor. In the testicle, more genes involved in the DNA damage signaling were downregulated during synthetic torpor. These data show for the first time that synthetic torpor is a radioprotector in non-hibernators, similarly to natural torpor in hibernating animals. Synthetic torpor can be an effective strategy to protect humans during long term space exploration of the solar system.