[P050] Measurement of the linear attenuation coefficients of breast tissues by synchrotron radiation computed tomography

Purpose: The aim of this paper is to investigate the limits of LET monitoring of therapeutic carbon ion beams with miniaturized microdosimetric detectors. Methods: Four different miniaturized microdosimeters have been used at the 62 MeV/u 12C beam of INFN Southern National Laboratory (LNS) of Catania for this purpose, i.e. a mini-TEPC and a GEM-microdosimeter, both filled with propane gas, and a silicon and a diamond microdosimeter. The y-D (dose-mean lineal energy) values, measured at different depths in a PMMA phantom, have been compared withLET¯D (dose-mean LET) values in water, calculated at the same water-equivalent depth with a Monte Carlo simulation setup based on the GEANT4 toolkit. Results: In these first measurements, no detector was found to be significantly better than the others as a LET monitor. The y-D relative standard deviation has been assessed to be 13% for all the detectors. On average, the ratio between y-D and LET¯D values is 0.9 ± 0.3, spanning from 0.73 ± 0.08 (in the proximal edge and Bragg peak region) to 1.1 ± 0.3 at the distal edge. Conclusions: All the four microdosimeters are able to monitor the dose-mean LET with the 11% precision up to the distal edge. In the distal edge region, the ratio of y-D to LET¯D changes. Such variability is possibly due to a dependence of the detector response on depth, since the particle mean-path length inside the detectors can vary, especially in the distal edge region. © 201

Parit\ue0 e Allattamento quali fattori protettivi di carcinoma mammario nelle donne triestine

Introduzione: Il ruolo dell\u2019allattamento come fattore protettivo nell\u2019insorgenza del carcinoma (ca) mammario trova posizioni contrastanti in letteratura. Questo studio analizza i fattori legati alla storia riproduttiva della donna per confrontare la realt\ue0 della popolazione femminile triestina rispetto a quanto proposto in letteratura. A Trieste l\u2019 incidenza standardizzata europea \ue8 di 148 nuove diagnosi di ca mammario all\u2019anno ogni 100.000 donne residenti, che \ue8 ben pi\uf9 alta della media italiana (105 nuovi casi, IARC 2006). Materiali e Metodi: Dal 2006 presso l\u2019unit\ue0 senologica della provincia di Trieste, a tutte le donne con patologia mammaria benigna e maligna e ad un ampio campione di donne sane, viene somministrato un questionario per valutare i fattori correlati all\u2019insorgenza di ca mammario per complessive 4307 donne (pari al 6.2% della popolazione femminile triestina). La casistica \ue8 stata suddivisa in base alla decade di nascita (1930-39,\u20261970-79) e sono state analizzate le variabili \u201cnumero figli\u201d, \u201cet\ue0 al primo parto\u201d e \u201callattamento\u201d. Inoltre \ue8 stato condotto uno studio retrospettivo caso-controllo per valutare l\u2019eventuale ruolo protettivo delle gravidanze e dell\u2019allattamento nell\u2019\u2019insorgenza del carcinoma, studio focalizzato sulle donne nate nel periodo 1930-1969 (\ue8 stata esclusa per scarsa numerosit\ue0 la decade 1970-79). Ogni caso \ue8 stato appaiato ad un controllo con lo stesso anno di nascita. Per l\u2019analisi statistica \ue8 stato utilizzato il software R. Risultati: Lo studio \ue8 rappresentativo degli importanti cambiamenti a livello \u201csociale\u201d registrati nel corso delle decadi: incremento delle donne nullipare (dal 15% al 27%) ed un aumento dell\u2019et\ue0 delle donne al primo parto, (da un\u2019et\ue0 mediana di 24 anni a 30 anni). L\u2019analisi conferma il dato, gi\ue0 segnalato dalla letteratura, che l\u2019avere avuto figli riduce, soprattutto per le donne pi\uf9 giovani, il rischio di ca mammario: per le nate negli anni 1950-1959 il rischio relativo (RR) \ue8 pari a 0.56 [0.39-0.97], che passa a 0.40 [0.21-0.74], per quelle nate negli anni 1960-69; la parit\ue0 invece, in accordo con la letteratura non \ue8 pi\uf9 un fattore rilevante nelle donne della classe 1930-1949. Nel nostro campione anche l\u2019allattamento risulta un fattore protettivo nelle donne in et\ue0 fertile (RR=0.30 [0.11-0.76] ) soprattutto se questo si protrae fino al 12\ub0 mese (RR=0.16 [0.06-0.44]). Al contrario, e in accordo con i dati di letteratura, l'allattamento non riduce il rischio di ca mammario dopo la menopausa. Discussioni e Conclusioni: Nello studio triestino, la parit\ue0 e l\u2019allattamento risultano fattori protettivi per il ca della mammella solo per le donne in et\ue0 fertile e, in accordo con la letteratura , non riscontra significativa protezione nelle donne in post menopausa

Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses.

The immune system plays a central role in the onset and progression of cancer. A better understanding of transcriptional changes in immune cell-related genes associated with cancer progression, and their significance in disease prognosis, is therefore needed. NanoString-based targeted gene expression profiling has advantages for deployment in a clinical setting over RNA-seq technologies. We analysed NanoString PanCancer Immune Profiling panel gene expression data encompassing 770 genes, and overall survival data, from multiple previous studies covering 10 different cancer types, including solid and blood malignancies, across 515 patients. This analysis revealed an immune gene signature comprising 39 genes that were upregulated in those patients with shorter overall survival; of these 39 genes, three (MAGEC2, SSX1 and ULBP2) were common to both solid and blood malignancies. Most of the genes identified have previously been reported as relevant in one or more cancer types. Using Cibersort, we investigated immune cell levels within individual cancer types and across groups of cancers, as well as in shorter and longer overall survival groups. Patients with shorter survival had a higher proportion of M2 macrophages and γδ T cells. Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival

Genes differentially expressed in short survival versus long survival patients, considered according to cancer type and cancer class.

Volcano plots showing significantly downregulated (the thresholds are FDR -0.5) genes in green and red, respectively. Here short survival patients are compared with long survival patients, so in all three panels genes found to be upregulated are genes that are upregulated in short survival patients, and genes found downregulated are genes that are downregulated in short survival patients. Grey indicates genes that are not significantly downregulated or upregulated. Log of fold change (LogFC) is on the x-axis and significance level (-log10P) is on the y-axis. Panel A shows differentially expressed genes when all of the patients are considered (n = 515). Panel B shows differentially expressed genes when only patients with solid cancers are considered (n = 293), and panel C shows differentially expressed genes when only patients with blood cancers are considered (n = 222). In all panels, the significantly downregulated and upregulated genes are labelled with their Hugo Gene Nomenclature Committee (HGNC) gene symbols. The three genes (SSX1, MAGEC2 and ULBP2) that are found to be significantly differentially expressed in all three analyses are shown in bold.</p

Patients statistics.

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