Comparison of carbon ion and photon reirradiation for recurrent glioblastoma

Purpose Purpose of this study was to investigate overall survival in recurrent glioblastoma treated with either carbon ion reirradiation or photon reirradiation. Materials and methods In this retrospective study we evaluated 78 consecutive patients with recurrent IDH (Isocitrate dehydrogenase)-wildtype glioblastoma (38 patients carbon ion re-radiotherapy, 40 patients photon re-radiotherapy) treated with either carbon ion reirradiation or stereotactic photon reirradiation. 45 Gy (RBE; 15 fractions) carbon ion reirradiation (CIRT) or 39 Gy (13 fractions) photon reirradiation (FSRT) was administered, respectively. Overall survival was investigated with respect to histological, clinical, and epidemiological features. Kaplan–Meier and multivariate Cox statistics were calculated. A propensity score-matched analysis of the FSRT and CIRT groups using variables from a validated prognosis score was carried out. Results The type of reirradiation (CIRT vs. FSRT) significantly influenced overall survival—8.0 months vs. 6.5 months (univariate: p = 0.046)—and remained an independent prognostic factor in multivariate analysis (p = 0.017). Propensity score-adjusted analysis with CIRT versus FSRT as the dependent variable yielded a significant overall survival advantage for the CIRT group (median OS 8.9 versus 7.2 months, p = 0.041, 1‑year survival 29 versus 10%). Adverse events (AE) were evaluated for both subgroups. For the FSRT group no toxicity ≥ grade 4 occurred. For the CIRT subgroup no grade 5 AE occurred, but 1 patient developed a grade 4 radionecrosis. We encountered 4 grade 3 toxicities. One patient developed a zoster at the trunk, 2 progressed in their paresis, and 1 featured progressive dysesthesia. Conclusion In conclusion, carbon ion treatment is a safe and feasible treatment option for recurrent glioblastoma. Due to the retrospective nature of the study and two different dose levels for CIRT or FSRT, the improved outcome in CIRT reirradiation might be an effect of higher biological impact from carbon ions or a simple dose-escalation effect. This hypothesis needs prospective testing in larger patient cohorts. A prospective phase III randomized trial is in preparation at our center.

A Mathematic Method to Adjust MLC Leaf End Position for Accuracy Dose Calculation in Carbon Ion Beam Radiation Therapy Treatment Planning System

IntroductionWe present a mathematic method to adjust the leaf end position for dose calculation correction in carbon ion radiation therapy treatment planning system. Methods and MaterialsA struggling range algorism of 400 MeV/n carbon ion beam in nine different multi-leaf collimator (MLC) materials was conducted to calculate the dose 50% point in order to derive the offset corrections in carbon ion treatment planning system (ciPlan). The visualized light field edge position in treatment planning system is denoted as Xtang.p and MLC position (Xmlc.p) is defined as the source to leaf end mid-point projection on axis for monitor unit calculation. The virtual source position of an energy at 400 MeV/n and struggling range in MLC at different field sizes were used to calculate the dose 50% position on axis. On-axis MLC offset (correction) could then be obtained from the position corresponding to 50% of the central axis dose minus the Xmlc.p MLC position. ResultsThe precise MLC position in carbon ion treatment planning system can be used an offset to do the correction. The offset correction of pure tungsten is the smallest among the others due to its shortest struggling range of carbon ion beam in MLC. The positions of 50% dose of all MLC materials are always located in between Xtang.p and Xmlc.p under the largest field of 12 cm by 12 cm. ConclusionsMLC offset should be adjusted carefully at different field size in treatment planning system especially of its small penumbra characteristic in carbon ion beam. It is necessary to find out the dose 50% position for adjusting MLC leaf edge on-axis location in the treatment planning system to reduce dose calculation error.

Transcriptome analysis provides insights into copper toxicology in piebald naked carp (Gymnocypris eckloni)

Background Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni. Results We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was “Ribosome” in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells. Conclusions Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.

Alleviation of Salinity Hazards in Different Maize Genotypes Using Inorganic Ions (Ca++ and K+)

A hydroponic experiment was conducted to evaluate and compare the efficiency of Ca and K ions and different maize genotypes with imposed salinity. Two levels of K+ and Ca++ (5 and 10 mM) each were tested on two maize genotypes (Pioneer-3335 and Syngenta-8441) under 100 mM NaCl stress. Saline treatment adversely affected the plant physiological parameters and disturbed the ionic balance and resulted in poor plant growth. However, Syngenta-8441 was more prone to salt stress as compared to Pioneer-3335. Both of the inorganic ions showed significant effects on physiological and ionic components of both genotypes. Among the inorganic ions K was found to be more efficient than Ca in improving the plant growth. Improved physiological and ionic traits were observed more significant with 10 mM K ion treatment followed by 5 mM K. Among Ca treatments higher level of Ca (10 mM) showed more significant results as compared to 5mM Ca++. This study revealed that Ca++ and K+ both are compulsory for maintaining the crop growth because of their mutual effects under salt stress. However, the alleviative efficiency of K is far better than Calcium but its (Ca++) role could not be neglected, while regarding genotypic differential response imposes the fact that Pioneer-3335 is more tolerant to salinity menace as compared to Syngenta- 8441 but both of the genotypes were significant in their recovery from stress to applied Ca++ and K+.