Influence of different Fletcher–Suit applicator geometries on sagittal dose distribution

IntroductionOne of the brachytherapy treatment modality of cervix carcinomas is insertion with Fletcher–Suit (FS) applicator. Depending on the patient anatomy and pathology and on the construction of the FS applicator different geometrical arrangements in ovoid separation, in ovoids' sagittal level with respect to the tandem were experienced. The multiple insertions show minor differences in applicator geometries. The aim of the study is to evaluate the influence of main geometrical parameters: the ovoid separation, symmetry and the ovoids' sagittal shift on dose distribution in different FS applicator arrangements. We tested the effect of dwell time settings in improvement of dose distribution of less adequate insertions. We also investigated the effect of inter-fractional variation of applicator geometry.Materials and methodsWe considered 73 treatment fractions of 22 patients. All insertions were performed by the same gynaecologist with the same type of FS applicator, while the treatment plans were generated by the same physicist using the same treatment planning method. We compared the sagittal dose distribution of different FS applicator geometries with dose levels at two applicator points, defined 2 cm apart from the tandem towards the bladder and rectum. We computed the Pearson correlation coefficients between the dose levels at the applicator points and the ovoid separation, symmetry and the ovoids' sagittal shift. We also investigated the effect of dwell time settings in ovoids in order to decrease the dose to organs at risk. The inter-fractional variation of the FS applicator geometries and the influence on the dose levels at the two applicator points were also tested.Results and conclusionsStrong correlation was found between the ovoid separation and dose values to applicator points defined in sagittal direction of FS applicator arrangements. Also strong correlation was between the ovoids' sagittal position with respect to the tandem and the applicator point defined towards the rectum, while the ovoid symmetry had no influence on the sagittal dose distribution. The standard deviations of inter-fractional variation of the ovoid separation and the ovoids' sagittal position were within ±5.2 mm and ±10.2 mm respectively. The inter-fractional variations in FS applicator geometry resulted in variation in dose levels at the applicator points ±0.8 Gy typically, while the largest value was ±1.6 Gy.     

Measurement verification of dose distributions in pulsed-dose rate brachytherapy in breast cancer

Aim

The aim of the study was to verify the dose distribution optimisation method in pulsed brachytherapy.

Background

The pulsed-dose rate brachytherapy is a very important method of breast tumour treatment using a standard brachytheraphy equipment. The appropriate dose distribution round an implant is an important issue in treatment planning. Advanced computer systems of treatment planning are equipped with algorithms optimising dose distribution.

Materials and methods

The wax-paraffin phantom was constructed and seven applicators were placed within it. Two treatment plans (non-optimised, optimised) were prepared. The reference points were located at a distance of 5 mm from the applicators’ axis. Thermoluminescent detectors were placed in the phantom at suitable 35 chosen reference points.

Results

The dosimetry verification was carried out in 35 reference points for the plans before and after optimisation. Percentage difference for the plan without optimisation ranged from −8.5% to 1.4% and after optimisation from −8.3% to 0.01%. In 16 reference points, the calculated percentage difference was negative (from −8.5% to 1.3% for the plan without optimisation and from −8.3% to 0.8% for the optimised plan). In the remaining 19 points percentage difference was from 9.1% to 1.4% for the plan without optimisation and from 7.5% to 0.01% for the optimised plan.No statistically significant differences were found between calculated doses and doses measured at reference points in both dose distribution non-optimised treatment plans and optimised treatment plans.

Conclusions

No statistically significant differences were found in dose values at reference points between doses calculated by the treatment planning system and those measured by TLDs. This proves the consistency between the measurements and the calculations.     

CT based conformal brachytherapy treatment planning

PURPOSE: To introduce the CT based three dimensional (3D) conformal brachytherapy treatment planning for interstitial implants, to compare the conventional X-ray film based planning with the 3D planning from the point of view of reconstruction and dosimetry, to discuss the differences and highlight the advantages. MATERIAL AND METHODS: On 10 patients with breast and 5 with head and neck tumor treated with HDR interstitial implants, following the catheter implantations, CT scans were taken at 5 mm spacing. The images were loaded into the PLATO BPS v14.0 3D planning system for brachytherapy. The contours of the target volume and critical structures were outlined on each slice, the catheter describing points were identified and the anatomical structures and catheter positions were reconstructed in 3D. Having taken into account the target volume, the active lengths were determined in each catheter, and dose optimization on dose points on target was performed. RESULTS: The 3D treatment planning was applied at interstitial breast treatments and head and neck implants. We investigated the dose distribution on axial, reconstructed coronal / sagittal planes and in 3D view with respect to anatomical structures. Dose volume histograms related to the target volume and critical structures were used for quantitative assessment of the plans. We found that the conformal dose distribution might result in increase of dose inhomogeneity within the target volume. CONCLUSIONS: The three dimensional brachytherapy treatment planning can be introduced into the clinical practice under proper technical conditions. A tradeoff between conformality and dose homogeneity results in an acceptable dose plan. The dose inhomogeneity can be decreased with the use of CT scans taken before the implantation. The guidelines and quantitative parameters describing the dose distribution, which can be used for determining the optimal dose distribution in clinical point of view, are still waiting to be established.     

Impact of Progerbalin LG® on the apple fruit physical attributes

During two consecutive years (2010 and 2011) we evaluated the impact of Progerbalin LG^® (mixture of gibberellins (GA₄₊₇) and N ⁶-benzyladenine) on fruit weight, fruit dimensions, elongation, geometric mean diameter or fruit size, aspect ratio, surface area and fruit volume of five apple cultivars belonging to ‘Red Delicious’ group (‘Hapke’ grafted on M.9 and M.26, ‘Hi Red’, ‘Starking’ and ‘Top Red’ on M.9, and ‘Red Chief Camspur’ on MM.106 rootstock). Trees were sprayed twice with 30, 50 or 100 ml L^?1 i.e. between 80 % of open flowers and the following petal fall (first treatment), and 10 days after first application (second treatment); control trees were not sprayed. Results showed that the lowest dose increased fruit weight in all cultivars, except ‘Top Red’ and ‘Red Chief Camspur’; this dose promoted fruit dimensions, fruit size and elongation in ‘Hapke’ on both rootstocks, and also fruit dimensions, surface area and fruit volume in ‘Hi Red’. Regarding ‘Starking’, different doses of Progerbalin LG^® did not affect other properties evaluated, but season played an important role in these cases. In contrast, the highest dose of this hormone improved all physical attributes in ‘Top Red’ and ‘Red Chief Camspur’, except elongation and/or aspect ratio. In some cases, good values were found in control treatment.     

Clinical examples of 3D dose distribution reconstruction,based on the actual MLC leaves movement,for dynamic treatment techniques

AimTo present practical examples of our new algorithm for reconstruction of 3D dose distribution, based on the actual MLC leaf movement.BackgroundDynaLog and RTplan files were used by DDcon software to prepare a new RTplan file for dose distribution reconstruction.Materials and methodsFour different clinically relevant scenarios were used to assess the feasibility of the proposed new approach: (1) Reconstruction of whole treatment sessions for prostate cancer; (2) Reconstruction of IMRT verification treatment plan; (3) Dose reconstruction in breast cancer; (4) Reconstruction of interrupted arc and complementary plan for an interrupted VMAT treatment session of prostate cancer. The applied reconstruction method was validated by comparing reconstructed and measured fluence maps. For all statistical analysis, the U Mann–Whitney test was used.ResultsIn the first two and the fourth cases, there were no statistically significant differences between the planned and reconstructed dose distribution (p = 0.910, p = 0.975, p = 0.893, respectively). In the third case the differences were statistically significant (p = 0.015). Treatment plan had to be reconstructed.ConclusionDeveloped dose distribution reconstruction algorithm presents a very useful QA tool. It provides means for 3D dose distribution verification in patient volume and allows to evaluate the influence of actual MLC leaf motion on the dose distribution.     

Growth response of Alstroemeria ‘Parigro Pink’ to phosphate supply in vitro

Rhizome tip explants of Alstroemeria ‘Parigo Pink’ were established on modified Murashige &; Skoog medium with P added as KH₂PO₄ at 0, 0.01, 0.05, 0.25, 1.25 or 2.5 mM. Cultures were transferred to fresh media every 4 weeks. Five explants were harvested from each P treatment after 3, 5, 7, 9 and 11 weeks in culture. Explants were separated into rhizome and shoot, weighed, dried and wet-ashed. Phosphorus content of the ash was determined colorimetrically. Explants supplied 1.25 or 2.5 mM P produced significantly more shoots and growing points, and greater fresh weight of rhizomes and shoots, than those provided with lower P concentrations. Phosphorus accumulation rates in shoots in the two highest P treatments were significantly greater than in the lower P treatments. Shoot tissue P concentrations greater than 7 mmol kg^-1 fwt evidently are required for maximum in vitro growth of Alstroemeria ‘Parigro Pink’. Explants provided the two highest P treatments partitioned a greater proportion of fresh weight and total P to shoots vs rhizomes than lower P treatments.     

Ecomorph Evolution in <Emphasis Type="Italic">Myotis</Emphasis> (Vespertilionidae,Chiroptera)

The genus Myotis is unique among mammals in its high taxonomic diversity and global distribution. Their phylogenetic relationships reflect biogeographic affinities rather than phenotypes. Myotis diverged from other bats in the early Miocene, with a subsequent split between Old and New World lineages about 19 million years ago. Similar ecomorphs (‘Leuconoe’ [near-water hunters], ‘Myotis’ [gleaners], ‘Selysius’ [aerial hawkers]) emerged independently in different lineages of Myotis. We retrieved the probable ancestral ecomorph for each lineage. Phenetic diversity was estimated from the analysis of body and skull traits. It seems that evolution of Myotis fluctuated between ‘Leuconoe’, ‘Selysius’, and larger ‘Myotis’.     

Does habitat use and ecological niche shift over the lifespan of wild species? Patterns of the bearded vulture population in the Western Alps

We analysed bearded vulture (Gypaetus barbatus) occurrences collected through long-term monitoring (from 1993 to 2010) in the Western Alps (1) to test whether ecological niches shift due to individual development and (2) to verify whether these patterns could reflect their spatial distribution. Thus, we compared the distribution patterns of three age classes (‘young’, ‘sub-adults’ and ‘adults’) through the K-select analysis. We then computed ten species distribution models (SDMs) and their average prediction to test for differences in age class distribution. The K-select analysis showed highly significant differences in the ecological niche among all the age classes and we also found highly significant differences in all the SDMs among the three age classes considered. Our results quantitatively showed that target species exhibits age specific shifts in the ecological niche and changes in the spatial distribution of individuals. Our methods are potentially widely applicable for testing differences among age classes of other species and thus, defining the best conservation actions (such as re-introduction) by taking into account different requirements in different stages of the individuals’ life.     

Epistatic fire blight resistance QTL alleles in the apple cultivar ‘Enterprise’ and selection X-6398 discovered and characterized through pedigree-informed analysis

Most cultivated apple cultivars are highly susceptible to fire blight, caused by Erwinia amylovora. However, differences in resistance levels are observed among cultivars and could be used in breeding. In this paper, we investigated the genetic basis of fire blight resistance of the cultivar ‘Enterprise’ and the advanced breeding selection X-6398. Genotyped pedigrees were used for validating and curating historic pedigree records. Various quantitative trait locus (QTL) discovery approaches were applied on the full-sib families ‘Gala’ × ‘Enterprise’ (GaEn) and X-6398 × X-6683 (IW) with the software FlexQTL? and MapQTL®. The paternal lineage of ‘Enterprise’ was reconstructed and showed to include ‘Cox’s Orange Pippin’. The QTLs found varied with the software used. Using FlexQTL?, two were found on linkage groups (LGs) 7 and 13, favourable alleles inherited by Enterprise from ‘Cox’s Orange Pippin’ and ‘Golden Delicious’, respectively. The former was identical to the previously named FB_F7 allele from ‘Fiesta’, while the latter is new and has been named FB_13GD. X-6398 had a QTL at the same position as FB_F7. Its favourable allele was new, originating from the unknown grandfather of X-4598, and was named FB_7X-6398. Using MapQTL® on GaEn, FB_F7 was also identified. Performing the same analysis on the subset of offspring that carried the favourable allele of FB_F7, two putative QTLs on LG8 and on top of LG13 were identified, which showed interactions with FB_F7. Implication of the findings for breeding for fire blight-resistant apples is discussed. Single nucleotide polymorphism data on Enterprise and its ancestors are provided.     

Protein expression patterns in two Spiraea species in response to cold treatment

We analyzed the different cold-resistance species Spiraea trichocarpa Nakai and Spiraea bumalda ‘Goldmound’ for low-temperature protein expression, protein types identification, and investigated the cold resistance mechanisms under different levels of low temperature by two-dimensional gel electrophoresis (2-DE) and mass spectrometry. An average of 668 and 559 protein spots were detected by 2-DE of S. bumalda ‘Goldmound’ and S. trichocarpa Nakai, respectively, under different low-temperature treatments. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy identified 48 proteins, with varying expression, related to metabolism, amino acid synthesis, transportation, stress responses and oxidation–reduction reactions. The results showed that the photosynthesis of S. bumalda ‘Goldmound’ had been affected, enzymes (RuBisCO large and small subunits) involved in the Calvin cycle were up- and down-regulated, and ATP synthase in photophosphorylation was down-regulated. Cytosolic malate dehydrogenase expression weakened in the TCA cycle, while amino acid synthesis strengthened. The activity of four antioxidant enzymes (superoxide dismutase [Cu–Zn], L-ascorbate peroxidase, glutathione peroxidase and peroxidase) was reduced under varying low temperatures. Enzymes (ribulose-bisphosphate carboxylase and RuBisCO small chain precursor) involved in the photosynthesis of S. trichocarpa Nakai showed obvious up- and down-regulation under low temperatures. Cold treatment influenced the photosynthesis of S. trichocarpa Nakai and S. bumalda ‘Goldmound’, but the results showed significant differences between the two species, which were supposed to the fact that low temperature modified the metabolic mechanisms and led to the weaker cold resistance in S. bumalda ‘Goldmound’ than in S. trichocarpa Nakai.     

Role of age and tumour stage in the temporal pattern of 'cure' from stomach cancer: a population-based study in Osaka, Japan

Objectives: To evaluate progress in stomach cancer care in Japan since 1975. Design: Population-based study of data extracted from the Osaka Cancer Registry. Setting: Population-based cancer registry in the area of Osaka Prefecture. Participants: All 66,032 cases diagnosed with a stomach cancer in Osaka Prefecture, Japan between 1975 and 2000 and registered in the Osaka Cancer Registry. Main outcome measures: ‘Cure’ fraction and median survival time for ‘uncured’ patients were estimated with multivariable mixture ‘cure’ model. The role played by age and stage at diagnosis on the changes in ‘cure’ parameters between 1975 and 2000 was evaluated. Missing stage was handled by multiple imputation approach. Results: More than 50% of the patients diagnosed with a stomach cancer in 1996–2000 were estimated ‘cured’ from their cancer, corresponding to a 20% increase since 1975–1980. Median survival time for ‘uncured’ patients however remained unchanged at about 8 months. ‘Cure’ fraction was over 85% for localised tumours and 30% for regional tumours, but stayed as low as 2.5% for distant metastatic cancers. Improvement was underestimated by about 10% because of ageing of cancer patients. Changes in stage distribution explained up to 40% of the increase in ‘cure’ fraction among men and up to 13% in women. Overdiagnosis was unlikely to play any role in these patterns. Conclusions: ‘Cure’ fraction from stomach cancer dramatically increased in Osaka, Japan since 1975, partly because of earlier stage at diagnosis, but mostly due to improvement in treatment of stomach cancer patients. This study, based on a leading country in term of stomach cancer management, provides insightful results for other countries in which ‘cure’ fraction is usually much lower.     

P300-like potentials in the normal monkey using classical conditioning and an auditory ‘oddball’ paradigm

Endogenous components of evoked potentials resembling P300 in humans were sequentially studied in 3 cynomolgus monkeys (Macaca fascicularis) using an auditory ‘oddball’ paradigm. The two different auditory stimuli were 500 Hz and 4000 Hz tones, designated as the ‘frequent’ and ‘rare’ stimuli, respectively. The probability of ‘rare’ tone presentation was initially 0.2. We further used probabilities of 0.1, 0.3 and 0.5. The ‘rare’ stimulus was reinforced by electrical stimulation, which followed the onset of the high tone by 700 msec. After 3–5 training sessions, a late positive wave was observed following the ‘rare’ tone. The latency of this P300-like signal was 314±16.2 msec, and teh amplitude 23.6±3.14 μV. The amplitude of this potential was modified by changes in stimulus presentation probability and by withholding reinforcement.     

Effects of arbuscular mycorrhizal inoculation on the growth,zinc distribution and photosynthesis of two citrus cultivars grown in low-zinc soil

Key message

‘Newhall’ and ‘Ponkan’ citrus cultivars grafted on trifoliate orange with mycorrhization by Glomus intraradices displayed different responses to low-Zn, and the optimal growth of ‘Newhall’ was more fungal inoculation dependent.

Abstract

The effects of arbuscular mycorrhizal (AM) fungus, Glomus intraradices, on plant growth, zinc (Zn) concentration and distribution, and photosynthesis were investigated in ‘Newhall’ navel orange (Citrus Sinensis) and ‘Ponkan’ tangerine (Citrus reticulata) grafted on the rootstock trifoliate orange (Poncirus trifoliata) exposed to low-Zn soil. Under the Zn-poor condition, the two cultivars showed similar decreases in growth, levels of leaf chlorophyll, gas exchange parameters, root soluble sugar, and Zn levels in various plant parts; however, the Zn percentage in the roots of ‘Ponkan’ was increased while in ‘Newhall’ it remained stable, indicating ‘Newhall’ may have a higher Zn translocation efficiency from the roots to the scion’s shoots. AM inoculation improved growth, Zn concentrations and photosynthesis in the two cultivars. AM-infected seedlings had lower minimal fluorescence values but higher maximal fluorescence values than non-infected seedlings. In addition, they were more efficient in terms of photosystem II’s (PS II’s) maximal and potential photochemistry. The greater changes appeared in ‘Newhall’, implying AM symbioses could alleviate the negative effects of low-Zn on the PS II reaction center. In addition, AM-infected ‘Newhall’ and ‘Ponkan’ seedlings had higher Zn percentages in the leaves but lower Zn ratios in the roots than non-AM-infected seedlings, especially in the former cultivar. These results indicate that G. intraradices has the potential to enhance the growth and Zn distribution in ‘Newhall’ grafted on trifoliate orange seedlings grown in low-Zn soil in a greenhouse.     

Biosynthetic processing of the oligosaccharide chains of cellular fibronectin

We have examined the maturation or processing of the oligosaccharides of cellular fibronectin in cultured chick embryo fibroblasts. Fibronectin was pulse-labeled with [2-³H]mannose or [³⁵S]methionine, and the turnover rates of carbohydrate and polypeptide portions of immunoprecipitated fibronectin were compared. The oligosaccharides on fibronectin were analyzed by gel electrophoresis for alterations in sensitivity to the enzyme endo-β-N-acetylglucosaminidase H, which specifically cleaves the ‘high-mannose’ class of asparagine-linked oligosaccharide. Incorporated mannose was removed only at early time points, suggesting that the structure of fibronectin oligosaccharides was altered due to processing.This possibility was confirmed by the analysis of glycopeptides generated by exhaustive pronase digestion. Two major glycopeptide structures were detected; their properties correspond to a ‘high-mannose’ oligosaccharide precursor and a ‘complex’ carbohydrate product. The precursor-product relationship of these two forms of oligosaccharide chains was demonstrated by pulse-chase labeling experiments. The precursor glycopeptide had an apparent size (M_r 2100) comparable to (Man)₉GlcNAc (M_r 2080), and was sensitive to endo-β-N-acetylglucosaminidase H; nearly all of the labeled mannose incorporated in a 10 min pulse was released from fibronectin glycopeptides by this enzyme. During a 90 min chase period, the glycopeptides became larger and increasingly resistent to endo-β-N-acetylglucosaminadase H cleavage. The final ‘complex’ or processed oligosaccharide structure contained approximately two-thirds less associated with the mature glycoprotein. They also indicate that the ‘complex’ structure is synthesized as a ‘high-mannose’ intermediate which is processed by the removal of mannose.     

Towards a better understanding of Lactobacillus rhamnosus GG - host interactions

Background

An industrial approach to protein production demands maximization of cloned gene expression, balanced with the recombinant host’s viability. Expression of toxic genes from thermophiles poses particular difficulties due to high GC content, mRNA secondary structures, rare codon usage and impairing the host’s coding plasmid replication. TaqII belongs to a family of bifunctional enzymes, which are a fusion of the restriction endonuclease (REase) and methyltransferase (MTase) activities in a single polypeptide. The family contains thermostable REases with distinct specificities: TspGWI, TaqII, Tth111II/TthHB27I, TspDTI and TsoI and a few enzymes found in mesophiles. While not being isoschizomers, the enzymes exhibit amino acid (aa) sequence homologies, having molecular sizes of ~120 kDa share common modular architecture, resemble Type-I enzymes, cleave DNA 11/9 nt from the recognition sites, their activity is affected by S-adenosylmethionine (SAM).

Results

We describe the taqIIRM gene design, cloning and expression of the prototype TaqII. The enzyme amount in natural hosts is extremely low. To improve expression of the taqIIRM gene in Escherichia coli (E. coli), we designed and cloned a fully synthetic, low GC content, low mRNA secondary structure taqIIRM, codon-optimized gene under a bacteriophage lambda (λ) P _R promoter. Codon usage based on a modified ‘one amino acid–one codon’ strategy, weighted towards low GC content codons, resulted in approximately 10-fold higher expression of the synthetic gene. 718 codons of total 1105 were changed, comprising 65% of the taqIIRM gene. The reason for we choose a less effective strategy rather than a resulting in high expression yields ‘codon randomization’ strategy, was intentional, sub-optimal TaqII in vivo production, in order to decrease the high ‘toxicity’ of the REase-MTase protein.

Conclusions

Recombinant wt and synthetic taqIIRM gene were cloned and expressed in E. coli. The modified ‘one amino acid–one codon’ method tuned for thermophile-coded genes was applied to obtain overexpression of the ‘toxic’ taqIIRM gene. The method appears suited for industrial production of thermostable ‘toxic’ enzymes in E. coli. This novel variant of the method biased toward increasing a gene’s AT content may provide economic benefits for industrial applications.     

Differential gene expression analysis of ‘Granny Smith’ apple (Malus domestica Borkh.) during fruit skin coloration

‘Granny Smith’ apples growing under normal sunlight develop green skin, whereas the peel turns red due to anthocyanin accumulation after the removal of a bagging treatment. Two anthocyanins, Cyanidin 3-O-galactoside (cy3-gal) and Cyanidin 3-O-arabinoside (cy3-ara), were detected in the red ‘Granny Smith’ apple peels, and cy3-gal was determined to be chiefly responsible for the red color. The content of cy3-gal was more than 98% of the total anthocyanin in the red ‘Granny Smith’ peels. To better understand the molecular basis of anthocyanin biosynthesis in ‘Granny Smith’ apples, we performed a quantitative real-time PCR (qRT-PCR) analysis of anthocyanin biosynthetic genes (MdCHS, MdF3H, MdDFR, MdANS, MdUFGT, and MdMYB1). Our results indicate that the expression of these genes (except MdCHS) was associated with increased anthocyanin accumulation in the skin of ‘Granny Smith’ apples. Four selected genes obtained from the ‘Granny Smith’ skin cDNA library, phytoene synthase (PSY), WD40 repeat protein, polygalacturonase (PG), and galactosidase (GAL), were also confirmed by qRT-PCR. We found that these genes were differently expressed during ‘Granny Smith’ apple skin coloration, suggesting that they are directly or indirectly involved in pigment accumulation. In conclusion, anthocyanin biosynthesis in ‘Granny Smith’ apples is the result of interactions between multiple enzymes in the anthocyanin biosynthesis pathway, and the coloring mechanism of ‘Granny Smith’ apples may be similar to that of red-skinned cultivars.     

Livistona palms in Australia: Ancient relics or opportunistic immigrants?

Eighteen of the 34 species of the fan palm genus Livistona (Arecaceae) are restricted to Australia and southern New Guinea, east of Wallace’s Line, an ancient biogeographic boundary between the former supercontinents Laurasia and Gondwana. The remaining species extend from SE Asia to Africa, west of Wallace’s Line. Competing hypotheses contend that Livistona is (a) ancient, its current distribution a relict of the supercontinents, or (b) a Miocene immigrant from the north into Australia as it drifted towards Asia. We have tested these hypotheses using Bayesian and penalized likelihood molecular dating based on 4 Kb of nuclear and chloroplast DNA sequences with multiple fossil calibration points. Ancestral areas and biomes were reconstructed using parsimony and maximum likelihood. We found strong support for the second hypothesis, that a single Livistona ancestor colonized Australia from the north about 10–17 Ma. Spread and diversification of the genus within Australia was likely favoured by a transition from the aseasonal wet to monsoonal biome, to which it could have been preadapted by fire-tolerance.     

Optimization of catheter’s implementation in the mold,in the case of vaginal HDR brachytherapy treatment

BackgroundThe purpose of this study was to evaluate and compare results obtained in high dose rate (HDR) brachytherapy treatment of vaginal cancer. Different catheters distributions inside the custom mold were explored. The difference between those distributions is the position of the posterior catheter located near the rectum in the actual custom mold applicator used in different hospitals, each one having a catheter displacement of 0.5 which is equal to the length of a step position. The best catheters distribution offering an optimal dose distribution: better coverage of the clinical target volume (CTV), while reducing the dose received by organs at risk (OARs), were discussed.Materials and methodsA group of 60 patients treated with HDR brachytherapy, alone or in combination with external radiotherapy, was investigated. A custom mold is normally used for HDR brachytherapy vaginal cancer treatment. Three different geometrical positions of the catheters (G1, G2 and G3) and, consequently, 3 different dosimetries were simulated out for each patient on the CT images, using the Oncentra planning system. The coverage of the CTV was studied.ResultsThe average volume treated was 30.46 cc (min = 9.8 cc, max = 70.86 cc). The total prescribed dose, including external and internal radiotherapy, was 80 Gy. We evaluated conformity index (CI), dose homogeneity index (DHI) and conformality index (COIN) indices for the three implantation geometries to reach the same coverage criteria of the CTV. The D2cc parameter allowed the evaluation of the dose received by the OARs. For the rectum, a dose reduction of 9.67% (range 0.29–32.86) was obtained with the second geometry of implantation compared to 10.14% (range 1.43–28.33) with the third geometry. For the bladder, the second geometry of implantation showed a better preservation for this organ [15.93% (range 0.86–58.71) vs. 8.35% (range 0.33–30.43) with the third geometry]. The sigmoid was more protected using the second plan of implantation as well [6.33% (range 0.14–40.71) for the second implantation compared to 5.95% (range 0.33–36) for the third implantation].ConclusionsG2 and G3 catheters’ distribution, having catheter position farther from the mold wall and so from the vaginal wall compared to the catheter position applied showed a better protection for the OARs while giving the same prescribed dose for the CTV.     

Find the path of least resistance: Adaptive therapy to delay treatment failure and improve outcomes

Cytotoxic chemotherapy and targeted therapies help people with advanced cancers, but for most, treatment fails. Cancer heterogeneity is one cause of treatment failure, but also suggests an opportunity to improve outcomes; reconceptualising cancer therapy as an ecological problem offers the strategy of adaptive therapy. If an agent is active against a patient's cancer, instead of traditional continuous dosing at the maximum tolerated dose until treatment failure, the patient and their oncologist may instead choose to pause treatment as soon as the cancer responds. When tumour burden increases, the cancer is rechallenged with the same agent in hope of delivering another response, ideally before symptoms occur or quality-of-life is impacted. These ‘loops’ of ‘pause/restart’ allows an active treatment to be used strategically, to delay the development of evolutionary selection within the cancer, delaying the onset of treatment resistance, controlling the cancer for longer. Modelling predicts patients can navigate several ‘loops’, potentially increasing the utility of an active treatment by multiples, and early trials suggest at least doubling of progression-free survival. In this narrative review we confront how cancer heterogeneity limits treatment effectiveness, re-examine cancer as an ecological problem, review the data supporting adaptive therapy and outline the challenges and opportunities faced in clinical practice to implement this evolutionary concept. In an era where multiple novel active anti-neoplastic agents are being used with ancient inflexibile maximum tolerated dose for maximum duration approaches, adaptive dosing offers a personalised, n = 1 approach to cancer therapy selection.