To compress or to breath-hold? A systematic review of the impact of motion mitigation techniques on motion, interfraction set-up errors, and intrafraction errors in patients with hepatobiliary and pancreatic malignancies

BACKGROUND AND PURPOSE: Reducing motion is vital in treating hepatobiliary (HPB) and pancreatic malignancies. Abdominal compression (AC) and breath-hold (BH) techniques aim to minimise respiratory motion, yet their adoption remains limited, and practices vary. This review examines the impact of AC and BH on motion, set-up errors, and patient tolerability in HPB and pancreatic patients. MATERIALS AND METHODS: This systematic review, conducted using PRISMA and PICOS criteria, includes publications from January 2015 to February 2023. Eligible studies focused on AC and BH interventions in adults with HPB and pancreatic malignancies. Endpoints examined motion, set-up errors, intra-fraction errors, and patient tolerability. Due to study heterogeneity, Synthesis Without Meta-Analysis was used, and a 5 mm threshold assessed the impact of motion mitigation. RESULTS: In forty studies, 14 explored AC and 26 BH, with 20 on HPB, 13 on pancreatic, and 7 on mixed cohorts. Six studied pre-treatment, 22 inter/intra-fraction errors, and 12 both. Six AC pre-treatment studies showed > 5 mm motion, and 4 BH and 2 AC studies reported > 5 mm inter-fraction errors. Compression studies commonly investigated the arch and belt, and DIBH was the predominant BH technique. No studies compared AC and BH. There was variation in the techniques, and several studies did not follow standardised error reporting. Patient experience and tolerability were under-reported. CONCLUSION: The results indicate that AC effectively reduces motion, but its effectiveness may vary. BH can immobilise motion; however, it can be inconsistent between fractions. The review underscores the need for larger, standardised studies and emphasizes the importance of considering the patient's perspective for tailored treatments

Navigating the straits: realizing the potential of proton FLASH through physics advances and further pre-clinical characterization

Ultra-high dose-rate ‘FLASH’ radiotherapy may be a pivotal step forward for cancer treatment, widening the therapeutic window between radiation tumour killing and damage to neighbouring normal tissues. The extent of normal tissue sparing reported in pre-clinical FLASH studies typically corresponds to an increase in isotoxic dose-levels of 5–20%, though gains are larger at higher doses. Conditions currently thought necessary for FLASH normal tissue sparing are a dose-rate ≥40 Gy s-1, dose-per-fraction ≥5–10 Gy and irradiation duration ≤0.2–0.5 s. Cyclotron proton accelerators are the first clinical systems to be adapted to irradiate deep-seated tumours at FLASH dose-rates, but even using these machines it is challenging to meet the FLASH conditions. In this review we describe the challenges for delivering FLASH proton beam therapy, the compromises that ensue if these challenges are not addressed, and resulting dosimetric losses. Some of these losses are on the same scale as the gains from FLASH found pre-clinically. We therefore conclude that for FLASH to succeed clinically the challenges must be systematically overcome rather than accommodated, and we survey physical and pre-clinical routes for achieving this

Influences on the Illusory Truth Effect in Consumer Judgment

The Illusory Truth Effect: Exploring Implicit and Explicit Memory Influences on Consumer JudgmentsMaria L. CronleyMiami UniversityFrank R. KardesUniversity of CincinnatiScott A. HawkinsUniversity of TorontoRepetition does not seem like a sound basis for determining truth, but researchers have consistently found that people rate repeated statements as more true than non-repeated statements. This effect is known as the illusory truth effect and appears to be quite persistent. Following on previous work in memory and judgment, additional moderators of attention, exclusion, and subliminal exposure are investigated in two experiments to assess their effects on repetition-induced beliefs of validity for product claims. Results provide new insights into the processes of incidental learning and implicit memory use by which consumers form judgments based on repetitive persuasive messages

Patient-reported outcomes in PROSPECT trial (Alliance N1048) – FOLFOX is not a panacea

The PROSPECT was a randomized phase III trial that included patients with resectable rectal cancer (clinical stage cT2-3N+ or cT3N0). The trial aimed to test the hypothesis that pre-operative chemotherapy consisting of 6 cycles of FOLFOX given over a 12-week period, followed by total mesorectal excision (TME) surgery, was non-inferior to pre-operative long-course chemoradiotherapy (CRT). The primary endpoint of the study was disease-free survival (DFS), and patients were also monitored for other relevant oncological outcomes such and health-related quality of life (HRQoL) using patient-reported outcome (PRO) tools [1, 2]

Stereotactic Body Radiotherapy re-irradiation for locally recurrent rectal cancer: outcomes and toxicity

Background: Stereotactic body radiotherapy (SBRT) has emerged as a potential therapeutic option for locally recurrent rectal cancer (LRRC) but contemporaneous clinical data is limited. We aimed to evaluate the local control, toxicity and survival outcomes in a cohort of patients previously treated with neoadjuvant pelvic radiotherapy for non-metastatic LRRC, now treated with SBRT. Methods: Inoperable rectal cancer patients with ≤ 3 sites of pelvic recurrence and > 6 months since prior pelvic radiotherapy were identified from a prospective registry over 4 years. SBRT dose was 30Gy in 5 fractions, daily or alternate days, using cumulative organ at risk dose constraints. Primary outcome was local control (LC). Secondary outcomes were progression free survival (PFS), overall survival (OS), toxicity and patient reported Quality of Life scores (QoL) using EQ-VAS tool. Results: 30 patients (35 targets) were included. Median GTV size was 14.3cm3. 27/30 (90%) previously received 45-50.4Gy in 25/28 fractions, with 10% receiving an alternative prescription. All patients received the planned re-irradiation SBRT dose. The median FU was 24.5 months (IQR 17.8 – 28.8). The 1-year LC was 84.9% (95% CI 70.6 – 99) and a 2-year LC was 69% (95% CI 51.8 – 91.9). The median PFS was 12.1 months (95% 8.6 – 17.66) and median OS was 28.3 months (95% CI 17.88 – 39.5 months). No patient experienced >G2 acute toxicity and only 1 patient experienced late G3 toxicity. Patient reported QoL outcomes were improved at 3 months following SBRT (Δ EQ-VAS, +10 points, Wilcoxon signed rank, p=0.009). Conclusion: Our study demonstrates that, for small volume pelvic disease relapses from rectal cancer, re-irradiation with 30Gy in 5 fractions is well tolerated and achieves an excellent balance between high local control rates with limited toxicity

Stereotactic body radiotherapy for moderately central and ultra-central oligometastatic disease: initial outcomes

Background: Delivery of SBRT to central thoracic tumours within 2 cm of the proximal bronchial tree (PBT), and especially ultra-central tumours which directly abut the PBT, has been controversial due to concerns about high risk of toxicity and treatment-related death when delivering high doses close to critical mediastinal structures. We present dosimetric and clinical outcomes from a group of oligometastatic patients treated with a risk-adapted SBRT approach. Methods: Between September 2015 and October 2018, 27 patients with 28 central thoracic oligometastases (6 moderately central, 22 ultra-central) were treated with 60 Gy in 8 fractions under online CBCT guidance. PTV dose was compromised where necessary to meet mandatory OAR constraints. Patients were followed up for toxicity and disease status. Results: Mandatory OAR constraints were met in all cases; this required PTV coverage compromise in 23 cases, with V100% reduced to <70% in 11 cases. No acute or late toxicities of Grade ≥ 3 were reported. One and 2 year in-field control rates were 95.2% and 85.7% respectively, progression-free survival rates were 42.8% and 23.4% respectively, and overall survival rates were 82.7% and 69.5% respectively. No significant differences were seen in control or survival rates by extent of PTV underdosage or between moderately and ultra-central cases. Conclusion: It appears that compromising PTV coverage to meet OAR constraints allows safe and effective delivery of SBRT to moderately and ultra-central tumours, with low toxicity rates and high in-field control rates. This treatment can be delivered on standard linear accelerators with widely available imaging technology

Response to growth hormone in patients with RNPC3 mutations

Peer reviewe

Understanding the individual to implement the ecosystem approach to fisheries management

Ecosystem-based approaches to fisheries management (EAFMs) have emerged as requisite for sustainable use of fisheries resources. At the same time, however, there is a growing recognition of the degree of variation among individuals within a population, as well as the ecological consequences of this variation. Managing resources at an ecosystem level calls on practitioners to consider evolutionary processes, and ample evidence from the realm of fisheries science indicates that anthropogenic disturbance can drive changes in predominant character traits (e.g. size at maturity). Eco-evolutionary theory suggests that human-induced trait change and the modification of selective regimens might contribute to ecosystem dynamics at a similar magnitude to species extirpation, extinction and ecological dysfunction. Given the dynamic interaction between fisheries and target species via harvest and subsequent ecosystem consequences, we argue that individual diversity in genetic, physiological and behavioural traits are important considerations under EAFMs. Here, we examine the role of individual variation in a number of contexts relevant to fisheries management, including the potential ecological effects of rapid trait change. Using select examples, we highlight the extent of phenotypic diversity of individuals, as well as the ecological constraints on such diversity. We conclude that individual phenotypic diversity is a complex phenomenon that needs to be considered in EAFMs, with the ultimate realization that maintaining or increasing individual trait diversity may afford not only species, but also entire ecosystems, with enhanced resilience to environmental perturbations. Put simply, individuals are the foundation from which population- and ecosystem-level traits emerge and are therefore of central importance for the ecosystem-based approaches to fisheries management

Reefs at Risk: A Map-Based Indicator of Threats to the Worlds Coral Reefs

This report presents the first-ever detailed, map-based assessment of potential threats to coral reef ecosystems around the world. "Reefs at Risk" draws on 14 data sets (including maps of land cover, ports, settle-ments, and shipping lanes), information on 800 sites known to be degraded by people, and scientific expertise to model areas where reef degradation is predicted to occur, given existing human pressures on these areas. Results are an indicator of potential threat (risk), not a measure of actual condition. In some places, particularly where good management is practiced, reefs may be at risk but remain relatively healthy. In others, this indicator underestimates the degree to which reefs are threatened and degraded.Our results indicate that:Fifty-eight percent of the world's reefs are poten-tially threatened by human activity -- ranging from coastal development and destructive fishing practices to overexploitation of resources, marine pollution, and runoff from inland deforestation and farming.Coral reefs of Asia (Southeastern); the most species-rich on earth, are the most threatened of any region. More than 80 percent are at risk (undermedium and high potential threat), and over half are at high risk, primarily from coastal development and fishing-related pressures.Overexploitation and coastal development pose the greatest potential threat of the four risk categories considered in this study. Each, individually, affects a third of all reefs.The Pacific, which houses more reef area than any other region, is also the least threatened. About 60 percent of reefs here are at low risk.Outside of the Pacific, 70 percent of all reefs are at risk.At least 11 percent of the world's coral reefs contain high levels of reef fish biodiversity and are under high threat from human activities. These "hot spot" areas include almost all Philippine reefs, and coral communities off the coasts of Asia, the Comoros, and the Lesser Antilles in the Caribbean.Almost half a billion people -- 8 percent of the total global population -- live within 100 kilometers of a coral reef.Globally, more than 400 marine parks, sanctuaries, and reserves (marine protected areas) contain coral reefs. Most of these sites are very small -- more than 150 are under one square kilometer in size. At least 40 countries lack any marine protected areas for conserving their coral reef systems

Quantitative Analysis of Radiation-Associated Parenchymal Lung Change

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible