Risk factors for secondary bladder cancer following prostate cancer radiotherapy

This review investigates the complex landscape of secondary bladder cancer (SBC) after radiotherapy for prostate cancer (PCa). External beam radiotherapy (EBRT) poses an increased risk for SBC, while brachytherapy seems to be associated with smaller increased risks for SBC due to its targeted radiation delivery, sparing the surrounding bladder tissue. Secondary cancers in the bladder are the most frequently diagnosed secondary cancers in the PCa patient population treated with radiotherapy. Patient-related factors are pivotal, with age emerging as a dual-edged factor. While advanced age is a recognized risk for bladder cancer, younger PCa patients exhibit higher susceptibility to radiation-induced cancers. Smoking, a well-established bladder cancer risk factor, increases this vulnerability. Studies highlight the synergistic effect of smoking and radiation exposure, amplifying the likelihood of genetic mutations and SBC. The latency period of SBC, which spans years to decades, remains a critical aspect. There is a strong dose-response relationship between radiation exposure and SBC risk, with higher doses consistently being associated with a higher SBC risk. While specific models for therapeutic radiation-induced SBC are lacking, insights from related studies, like the Atomic Bomb survivor research, emphasize the bladder’s sensitivity to radiation-induced cancer. Chemotherapy in combination with radiotherapy, although infrequently used in PCa, emerges as a potential risk for bladder cancer. Bladder cancer’s complex epidemiology, encompassing risk factors, treatment modalities, and cancer types, provides a comprehensive backdrop. As research refines understanding, we hope that this review contributes to guide clinicians, inform patient care, and shape preventive strategies on SBC.</p

Benefits of using biosolid nutrients in Australian agriculture - a national perspective.

Increased nutrient levels in inland waterways have led to algal blooms and eutrophication in many agricultural regions. To ensure fertiliser inputs are managed more effectively, the source of contamination needs to be tracked and identified. Point sources could include inorganic fertilisers, livestock excreta, or more recently biosolids. The presence of faecal indicator microorganisms has been widely used to identify the presence of faeces, however, these methods cannot distinguish between human and animals samples. This study investigated PCR amplification as a molecular method to distinguish biosolids from livestock faeces of biosolids, cattle, sheep, poultry and kangaroo. This was achieved using published priming sequences and restriction site profiling of amplified DNA across the 16S rRNA gene of anaerobic gastrointestinal bacteria Bacteroides spp and Bifidobacteria spp. Preliminary investigation showed that of the three Bacteroides spp primer pairs investigated, two were useful for cow faecal material; though at lower annealing temperatures were also applicable to biosolids and sheep faecal material. The third primer pair was specific only for biosolids. All three primer pairs were unable to PCR-amplify Bacteroides spp sequences in faecal material of kangaroo. Of the three Bifidobacteria spp primer pairs, one was useful for sheep faecal material; though at lower annealing temperature was also applicable to biosolids and cow and kangaroo faecal material. The Bifidobacterium angulatum specific primer pair enabled the PCR detection of anaerobes only in biosolids and faecal material of kangaroo. The third, a Bifidobacterium catenulatum specific primer pair was suitable for faecal material of cow and at lower annealing temperatures was also applicable to the sample from sheep. Varying degrees of success were observed in faecal material from other animals. Generally, biosolids tested positive for Bacteroides and Bfidobacteria with all primers except for those specific for B. angulatum. For some primer sets, PCR amplification alone could not differentiate biosolids from other faecal samples. The serial dilution of water contaminated by a range of livestock excreta and biosolids is being examined further to enable the sensitivity of this method to be applied in the field.Soil acidification is an increasing problem throughout many agricultural regions in Australia typically on lighter-textured soils that have a low buffering capacity to changes in soil pH and/or that may be naturally acidic. Crops and pastures grown on acidic soils are subject to problems such as aluminium toxicity (particularly in the subsoil), nodulation failure in legumes and a reduced availability of some nutrients. Lime and dolomite are products that are commonly applied to neutralise soil acidity and improve plant productivity with application rates often determined by their neutralising value and particle size of the product, and the pH buffering capacity (lime requirement) of the soil. To investigate the effect of lime amended biosolids (LAB) as a product for neutralising soil acidity and for improving crop growth, four rates of LAB (0, 5, 10 and 15 t DS/ha) and four equivalent rates of lime product (0, 2.3, 4.6 and 6.7 t/ha) were applied to an acidic red/brown sandy loam in the central wheatbelt of Western Australia. In addition, one rate of dewatered biosolids cake (DBC) at 7 t DS/ha was included to enable comparison to be made to this product. The experiment was conducted over three years and sown to wheat (Triticum aestivum), canola (Brassica napus) and then wheat in 2005, 2006 and 2007, respectively. Plants were sampled at 8 weeks and at harvest to determine the effect of LAB, lime and DBC on crop growth, nutrient uptake and grain yield. Samples of surface soil (0-10 cm) were collected and analysed at harvest for pH and major nutrients. Soil pH increased significantly with increasing rates of LAB or lime at the end of the first year, with similar values recorded between equivalent values of lime product. There was no significant change in soil pH following the addition of the DBC treatment. No further changes in soil pH had occurred by the end of the second year. The growth of both wheat and canola in the first two years was affected to a greater extent by nutrients (typically nitrogen) in the LAB than by the reduction in soil acidity. Measurements on wheat yield in the third year of the experiment and changes in soil pH in the surface (0-10 cm) and subsoil (10-20 cm) will provide further information as to the long term effects of LAB in agriculture and allow recommendations to be made regarding best practise land application rates

Biological and chemical assessment of zinc ageing in field soils

As zinc (Zn) is both an essential trace element and potential toxicant, the effects of Zn fixation in soil are of practical significance. Soil samples from four field sites amended with ZnSO4 were used to investigate ageing of soluble Zn under field conditions over a 2-year period. Lability of Zn measured using 65Zn radioisotope dilution showed a significant decrease over time and hence evidence of Zn fixation in three of the four soils. However, 0.01 M CaCl2 extractions and toxicity measurements using a genetically modified lux-marked bacterial biosensor did not indicate a decrease in soluble/bioavailable Zn over time. This was attributed to the strong regulatory effect of abiotic properties such as pH on these latter measurements. These results also showed that Zn ageing occurred immediately after Zn spiking, emphasising the need to incubate freshly spiked soils before ecotoxicity assessments. Ageing effects were detected in Zn-amended field soils using 65Zn isotopic dilution as a measure of lability, but not with either CaCl2 extractions or a lux-marked bacterial biosensor

Modelling the toxicity of copper and zinc to wheat and other crops and incorporation of the results into a proposed framework to derive biosolids guidelines

The application of biosolids to land can have both beneficial and detrimental environmentaleffects. The positive effects can arise from nutrients and organic carbon in the biosolids whilethe negative effects generally arise because of the contamination associated with biosolids(e.g. Broos et al., 2006; Heemsbergen et al., 2006; McLaughlin et al., 2006) but can also arisedue to excessive ammonia (Whatmuff et al., 2006). Therefore, any regulatory guidelinesdeveloped to manage the land application of biosolids must be able to enhance the beneficialeffects and minimise the deleterious effects

Effects of biosolids application on pasture and grape vines in south-eastern Australia

Biosolids were applied to a pasture and a vineyard in south-eastern Australia. At both sites, soil Cd, Cu, and Zn concentrations linearly increased with biosolids application rates although not to the extent of exceeding soil quality guidelines. Biosolids marginally increased soil C and N concentrations at the pasture site but significantly increased P concentrations. With lower overall soil fertility at the vineyard, biosolids increased C, N, and P concentrations. At neither site did biosolids application affect soil microbial endpoints. Biosolids increased pasture production compared to the unfertilised control but had little effect on grape production or quality. Interestingly, over the 3-year trial, there was no difference in pasture production between the biosolids treated plots and plots receiving inorganic fertiliser. These results suggest that biosolids could be used as a fertiliser to stimulate pasture production and as a soil conditioner to improve vineyard soils in this regio

Acute toxicity patterns and their management after moderate and ultra- hypofractionated radiotherapy for prostate cancer:A prospective cohort study

Objective: Hypofractionation has become the new clinical standard for prostate cancer. We investigated the management of acute toxicity in patients treated with moderate hypofractionation (MHF) or Ultrahypofractionation (UHF). Methods: In a prospective cohort setting, patients (N=316) received either MHF (20 fractions of 3/3.1 Gy, 5 fractions per week, N=156) or UHF (7 fractions of 6.1 Gy, 3 fractions per week, N=160) to the prostate +/- (base of the) seminal vesicles between 2019 and 2023. UHF was not indicated in case of significant lower urinary tract symptoms (LUTS) or T3b disease. Patient-reported outcomes (PRO) were online distributed at baseline, end of treatment (aiming at last fraction +/- 3 days), 3 months. Acute toxicity rates, management, and associations with baseline factors were analysed using Chi-square test and logistic regression. CTCAE scores (version 5) were calculated. Results: Treatment for acute urinary complaints was prescribed in 46 % (MHF) and 29 % (UHF). Taking into consideration baseline LUTS, MHF and UHF showed similar rates of PROs and management. Medication for acute gastrointestinal (GI) symptoms was prescribed for 21.1 % (MHF) and 14.1 % (UHF) with more loperamide for diarrhea in MHF (9.0 %) vs UHF (1.9 %, p = 0.005). Grade ≥ 2 (MHF / UHF) was scored in 40 % / 28 % for GI (p = 0.03) and 50 % / 31 % for GU (p &lt; 0.01). PROs for GI reported after last fraction of UHF were significantly worse compared to before last fraction. Conclusion: UHF was safe with respect to acute toxicity risks in the selected population. MHF is associated with risks of significant diarrhea which needs further investigation. Furthermore, optimal registration of acute toxicity for UHF requires measurements up to 1–2 weeks after the last fraction.</p

Predictive Factors for Toxicity After Primary Chemoradiation for Locally Advanced Cervical Cancer:A Systematic Review

Purpose: Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue complication probability (NTCP) models quantify toxicity risk and aid in optimizing radiation therapy to minimize side effects. However, it is unclear which predictors to include in an NTCP model. The aim of this systematic review was to provide an overview of the identified predictors contributing to gastrointestinal (GI), genitourinary (GU), and vaginal toxicities and insufficiency fractures for LACC. Methods and Materials: A systematic search was performed and articles evaluating the relationship between predictors and toxicities in women with LACC treated with primary chemoradiation were included. The Quality In Prognosis Studies tool was used to assess risk of bias, with high-risk studies being excluded from further analysis. Relationships between dose-volume parameters, patient and treatment characteristics, and toxicity endpoints were analyzed. Results:Seventy-three studies were identified. Twenty-six had a low or moderate risk of bias and were therefore included. Brachytherapy-related dose-volume parameters of the GI tract, including rectum and bowel equivalent dose in 2 Gy fractions (EQD2) D2 cm3, were frequently related to toxicities, unlike GU dose-volume parameters. Furthermore, (recto)vaginal point doses predicted toxicities. Few studies evaluated external beam radiation therapy dose-volume parameters and identified rectum EQD2 V30 Gy, V40 Gy, and V55 Gy, bowel and bladder EQD2 V40 Gy as toxicity predictors. Also, total reference air kerma and vaginal reference length were associated with toxicities. Relationships between patient characteristics and GI toxicity were inconsistent. The extent of vaginal involvement at diagnosis, baseline symptoms, and obesity predicted GU or vaginal toxicities. Only 1 study evaluated insufficiency fractures and demonstrated lower pretreatment bone densities to be associated. Conclusions: This review detected multiple candidate predictors of toxicity. Larger studies should consider insufficiency fractures, assess dose levels from external beam radiation therapy, and quantify the relationship between the predictors and treatment-related toxicities in women with LACC to further facilitate NTCP model development for clinical use.</p

Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy:A retrospective cohort study

Objectives:Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methods: This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60–70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. Results: The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p &lt; 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. Conclusion: Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.</p

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability