On the new metrics for IMRT QA verification

Purpose: the aim of this work is to search for new metrics that could give more reliable acceptance/ rejection criteria on the IMRT verification process and to offer solutions to the discrepancies found among different conventional metrics. Therefore, besides conventional metrics, new ones are proposed and evaluated with new tools to find correlations among them. These new metrics are based on the processing of the dosevolume histogram information, evaluating the absorbed dose differences, the dose constraint fulfillment, or modified biomathematical treatment outcome models such as tumor control probability (TCP) and normal tissue complication probability (NTCP). An additional purpose is to establish whether the new metrics yield the same acceptance/rejection plan distribution as the conventional ones. Methods: Fifty eight treatment plans concerning several patient locations are analyzed. All of them were verified prior to the treatment, using conventional metrics, and retrospectively after the treatment with the new metrics. These new metrics include the definition of three continuous functions, based on dosevolume histograms resulting from measurements evaluated with a reconstructed dose system and also with a Monte Carlo redundant calculation. The 3D gamma function for every volume of interest is also calculated. The information is also processed to obtain dTCP or dNTCP for the considered volumes of interest. These biomathematical treatment outcome models have been modified to increase their sensitivity to dose changes. A robustness index from a radiobiological point of view is defined to classify plans in robustness against dose changes. Results: Dose difference metrics can be condensed in a single parameter: the dose difference global function, with an optimal cutoff that can be determined from a receiver operating characteristics (ROC) analysis of the metric. It is not always possible to correlate differences in biomathematical treatment outcome models with dose difference metrics. This is due to the fact that the dose constraint is often far from the dose that has an actual impact on the radiobiological model, and therefore, biomathematical treatment outcome models are insensitive to big dose differences between the verification system and the treatment planning system. As an alternative, the use of modified radiobiological models which provides a better correlation is proposed. In any case, it is better to choose robust plans from a radiobiological point of view. The robustness index defined in this work is a good predictor of the plan rejection probability according to metrics derived from modified radiobiological models. The global 3D gamma-based metric calculated for each plan volume shows a good correlation with the dose difference metrics and presents a good performance in the acceptance/rejection process. Some discrepancies have been found in dose reconstruction depending on the algorithm employed. Significant and unavoidable discrepancies were found between the conventional metrics and the new ones. Conclusions: The dose difference global function and the 3D gamma for each plan volume a e good classifiers regarding dose difference metrics. ROC analysis is useful to evaluate the predictive power of the new metrics. The correlation between biomathematical treatment outcome models and the dose difference-based metrics is enhanced by using modified TCP and NTCP functions that take into account the dose constraints for each plan. The robustness index is useful to evaluate if a plan is likely to be rejected. Conventional verification should be replaced by the new metrics, which are clinically more relevant

Treatment of cervical cancer with electronic brachytherapy

Purpose: We report the first cervical cancer cases treated with interstitial electronic brachytherapy (eBT) at our hospital and compare them with plans made with high-dose-rate interstitial brachytherapy based on Ir192 (HDR-BT). Materials and methods: Eight patients with cervical cancer were treated with the Axxent eBT device (Xoft, Inc.). Planning was with magnetic resonance imaging and computed tomography following the recommendations of the EMBRACE protocol. The dosimetry parameters of organs at risk (OAR) were evaluated for the bladder, rectum, and sigmoid colon (D2cc, D1cc, and D0.1cc). In addition, the V150 and V200 of irradiated tissue were compared for both eBT and HDR-BT. All patients received intensity-modulated external beam radiation therapy with a regimen of 23 sessions of 2 Gy followed by four sessions of 7 Gy of eBT performed over 2 weeks (two sessions followed by another two sessions a week later) following the EMBRACE recommendations. Each of the eight patients was followed to assess acute toxicity associated with treatment. Results: The doses reaching OAR for eBT plans were lower than for HDR-BT plans. As for acute toxicity associated with eBT, very few cases of mucositis were detected. No cases of rectal toxicity and one case with grade 1 urinary toxicity were detected. The results at 1 month are equally good, and no relapses have occurred to date. Conclusions: The first results of treatment with the Axxent eBT device are promising, as no recurrences have been observed and toxicity is very low. eBT is a good alternative for treating cervical cancer in centers without access to conventional HDR

Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía

El PIMCD “Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía” constituye la cuarta edición de un PIMCD que ha recibido financiación en las últimas convocatorias de PIMCD UCM, de los que se han derivado actividades de formación para estudiantes de Grado, Máster y Doctorado y al menos 3 publicaciones colectivas publicadas por Ediciones Complutense, Siglo XXI y Palgrave McMillan

Treatment of cervical cancer with electronic brachytherapy

Purpose: We report the first cervical cancer cases treated with interstitial electronic brachytherapy (eBT) at our hospital and compare them with plans made with high-dose-rate interstitial brachytherapy based on Ir192 (HDR-BT). Materials and methods: Eight patients with cervical cancer were treated with the Axxent eBT device (Xoft, Inc.). Planning was with magnetic resonance imaging and computed tomography following the recommendations of the EMBRACE protocol. The dosimetry parameters of organs at risk (OAR) were evaluated for the bladder, rectum, and sigmoid colon (D2cc, D1cc, and D0.1cc). In addition, the V150 and V200 of irradiated tissue were compared for both eBT and HDR-BT. All patients received intensity-modulated external beam radiation therapy with a regimen of 23 sessions of 2 Gy followed by four sessions of 7 Gy of eBT performed over 2 weeks (two sessions followed by another two sessions a week later) following the EMBRACE recommendations. Each of the eight patients was followed to assess acute toxicity associated with treatment. Results: The doses reaching OAR for eBT plans were lower than for HDR-BT plans. As for acute toxicity associated with eBT, very few cases of mucositis were detected. No cases of rectal toxicity and one case with grade 1 urinary toxicity were detected. The results at 1 month are equally good, and no relapses have occurred to date. Conclusions: The first results of treatment with the Axxent eBT device are promising, as no recurrences have been observed and toxicity is very low. eBT is a good alternative for treating cervical cancer in centers without access to conventional HDR

Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling

Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. However, only a limited number of target genes have been identified. We have studied 10 MCL cell lines and 28 primary tumors with a combination of a high-density single-nucleotide polymorphism array and gene expression profiling. We detected highly altered genomes in the majority of the samples with a high number of partial uniparental disomies (UPDs). The UPD at 17p was one of the most common, and it was associated with TP53 gene inactivation. Homozygous deletions targeted 4 known tumor suppressor genes (CDKN2C, BCL2L11, CDKN2A, and RB1) and 6 new genes (FAF1, MAP2, SP100, MOBKL2B, ZNF280A, and PRAME). Gene amplification coupled with overexpression was identified in 35 different regions. The most recurrent amplified regions were 11q13.3-q13.5, 13q31.3, and 18q21.33, which targeted CCND1, C13orf25, and BCL2, respectively. Interestingly, the breakpoints flanking all the genomic alterations, including UPDs, were significantly associated with genomic regions enriched in copy number variants and segmental duplications, suggesting that the recombination at these regions may play a role in the genomic instability of MCL. This integrative genomic analysis has revealed target genes that may be potentially relevant in MCL pathogenesis