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

A tool to balance benefit and harm when deciding about adjuvant therapy

Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary. This study presents a scheme balancing benefit and harm of adjuvant therapy vs no adjuvant therapy. It is illustrated by the available evidence on adjuvant pelvic external beam radiotherapy (RT) for intermediate-risk stage I endometrial carcinoma patients. The scheme comprises five outcome possibilities of adjuvant therapy: patients who benefit from adjuvant therapy (some at the cost of complications) vs those who neither benefit nor contract complications, those who do not benefit but contract severe complications, or those who die. Using absolute risk differences, a fictive cohort of 1000 patients receiving adjuvant RT is categorised. Three large randomised clinical trials were included. Recurrences will be prevented by adjuvant RT in 60 patients, a majority of 908 patients will neither benefit nor suffer severe radiation-induced harm but 28 patients will suffer severe complications due to adjuvant RT and an expected four patients will die. This scheme readily summarises the different possible treatment outcomes and can be of practical value for clinicians and patients in decision making about adjuvant therapies

A room‐based diagnostic imaging system for measurement of patient setup

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135081/1/mp8461.pd

Numerical simulation of explosive volcanic eruptions from the conduit flow to global atmospheric scales

Volcanic eruptions are unsteady multiphase phenomena, which encompass many inter-related processes across the whole range of scales from molecular and microscopic to macroscopic, synoptic and global. We provide an overview of recent advances in numerical modelling of volcanic effects, from conduit and eruption column processes to those on the Earth s climate. Conduit flow models examine ascent dynamics and multiphase processes like fragmentation, chemical reactions and mass transfer below the Earth surface. Other models simulate atmospheric dispersal of the erupted gas-particle mixture, focusing on rapid processes occurring in the jet, the lower convective regions, and pyroclastic density currents. The ascending eruption column and intrusive gravity current generated by it, as well as sedimentation and ash dispersal from those flows in the immediate environment of the volcano are examined with modular and generic models. These apply simplifications to the equations describing the system depending on the specific focus of scrutiny. The atmospheric dispersion of volcanic clouds is simulated by ash tracking models. These are inadequate for the first hours of spreading in many cases but focus on long-range prediction of ash location to prevent hazardous aircraft - ash encounters. The climate impact is investigated with global models. All processes and effects of explosive eruptions cannot be simulated by a single model, due to the complexity and hugely contrasting spatial and temporal scales involved. There is now the opportunity to establish a closer integration between different models and to develop the first comprehensive description of explosive eruptions and of their effects on the ground, in the atmosphere, and on the global climate

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m−2), doxorubicin (45 mg m−2), cyclophosphamide (600 mg m−2) every 28 days for five cycles, or external RT (45–50 Gy on a 5 days week−1 schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66–1.36; P=0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63–1.23; P=0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited

Effect of octanoic acid-rich formula on plasma ghrelin levels in cachectic patients with chronic respiratory disease

<p>Abstract</p> <p>Background</p> <p>For cachectic patients with chronic respiratory disease (CRD), conventional enteral nutrition formula is an optional treatment to maintain energy balance. The molecular mechanisms by which enteral nutrition formula controls appetite and weight remain unknown. We examined whether enteral nutrition formula rich in octanoic acids would increase plasma levels of ghrelin, an appetite-stimulating hormone produced in the stomach, in cachectic patients with CRD.</p> <p>Methods</p> <p>Plasma ghrelin profiles in cachectic patients with CRD were assessed and compared with those in age- and sex-matched controls. Plasma levels of acyl-ghrelin, an active ghrelin modified by octanoic acids, and desacyl-ghrelin were measured separately. We examined changes in 24-h plasma ghrelin profiles before and after single administration of the formula. We also evaluated the effects of 2-week administration of the formula on plasma ghrelin levels and nutritional status in patients.</p> <p>Results</p> <p>The ratio of acyl-ghrelin to desacyl-ghrelin in plasma was lower in patients than in controls. Single administration of the formula did not change plasma desacyl-ghrelin levels, but induced an increase in acyl-ghrelin levels. Two-week treatment with the formula was effective in increasing weight and acyl-ghrelin, along with improving nutritional status in patients.</p> <p>Conclusion</p> <p>These results show that the formula contributes to increased weight, which may be associated with induction of acyl-ghrelin production in cachectic patients with CRD.</p

Automated causal inference in application to randomized controlled clinical trials

Randomized controlled trials (RCTs) are considered the gold standard for testing causal hypotheses in the clinical domain; however, the investigation of prognostic variables of patient outcome in a hypothesized cause–effect route is not feasible using standard statistical methods. Here we propose a new automated causal inference method (AutoCI) built on the invariant causal prediction (ICP) framework for the causal reinterpretation of clinical trial data. Compared with existing methods, we show that the proposed AutoCI allows one to clearly determine the causal variables of two real-world RCTs of patients with endometrial cancer with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remains consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis