A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

Background Bone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic. Methods This is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24-48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode. Discussion If a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures. Trial registration: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials. gov (NCT03831243) on February 5th 2019

Effets de l’environnement de vie sur les associations entre déterminants individuels et santé périnatale en Wallonie (Belgique)

Résumé L’association entre les caractéristiques individuelles des mères et la prématurité ou le faible poids à la naissance, tout comme l’effet de l’environnement de vie sur la santé périnatale ont fait l’objet de nombreux travaux. Plus rares sont les études qui se sont penchées sur l’effet que l’environnement de vie pouvait avoir sur l’association entre ces caractéristiques individuelles et la santé périnatale. Dans cet article, nous adoptons une perspective multi-niveaux pour prendre en compte conjointement l’effet de l’environnement de vie et les déterminants individuels des mères sur deux indicateurs de santé périnatale, la prématurité et le faible poids à la naissance en Wallonie. Les analyses portent sur 147 718 naissances vivantes uniques issues de mères qui résidaient en Wallonie de 2010 à 2013. Les variables indépendantes principales sont le niveau d’instruction, le statut professionnel et l’état de cohabitation des mères. Les variables dépendantes sont la prématurité et le faible poids à la naissance. Un indice synthétique des conditions de bien-être (ICBE) est utilisé pour décrire l’environnement de vie et mis en relation avec la prématurité et le faible poids à la naissance grâce à des modèles de régression logistique multivariables à un et plusieurs niveaux. La fréquence de la prématurité et du faible poids s’avère plus élevée dans les communes avec un environnement de vie défavorisé. Les mères ayant un faible niveau d’instruction, n’ayant pas d’activité professionnelle ou déclarant vivre seule courent par ailleurs un risque plus élevé d’accoucher prématurément ou d’avoir un enfant de faible poids à la naissance. Dans les analyses multi-niveaux, les mesures d’association entre les variables socio-économiques de la mère et les deux variables dépendantes restent identiques aux mesures d’association observées dans les régressions classiques. Les conditions de bien-être dans une commune, mesurées par l’ICBE, n’ont pas d’effet additionnel sur les associations entre les caractéristiques socio-économiques de la mère et la prématurité ou le faible poids à la naissance. Abstract The association between the individual characteristics of mothers, preterm birth or low birth weight and the impact of the living environment on perinatal health have been widely studied. Far fewer studies have examined the way the living environment can influence the association between characteristics and perinatal health. In this paper, we adopt a multi-level analysis to simultaneously study the effects of the living environment and the individual characteristics of the mothers on preterm birth and low-birth weight in Wallonia. The study population consists of 147’718 single live births to mothers who resided in Wallonia and delivered between 2010 and 2013. The main independent variables are the mothers’s level of education, their occupational and cohabitation status. The dependent variables are preterm birth and low birth weight. A synthetic index of Well-being condition (ICBE) is used to describe living conditions. The association between these conditions, preterm birth and low birth weight is quantified through multilevel logistic regression models adjusted for mothers’ characteristics. Preterm birth and low birth weight rates are higher in municipalities with a poor living environment. Non-working, single mothers or with low levels of education are at higher risk of delivering a preterm or low birth weight baby. In the multilevel analyses, the association between the socio-economic variables and the two dependent variables is similar to the one observed in the classical regressions (one level-analysis). Well-Being conditions, measured through ICBE, have no additional effect on the association between individual socio-economic characteristics of the mother, preterm birth or low birth weight.&nbsp

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial

BACKGROUND The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months

Model calibration of pharmacokinetic-pharmacodynamic lung tumour dynamics for anticancer therapies

Individual curves for tumor growth can be expressed as mathematical models. Herein we exploited a pharmacokinetic-pharmacodynamic (PKPD) model to accurately predict the lung growth curves when using data from a clinical study. Our analysis included 19 patients with non-small cell lung cancer treated with specific hypofractionated regimens, defined as stereotactic body radiation therapy (SBRT). The results exhibited the utility of the PKPD model for testing growth hypotheses of the lung tumor against clinical data. The model fitted the observed progression behavior of the lung tumors expressed by measuring the tumor volume of the patients before and after treatment from CT screening. The changes in dynamics were best captured by the parameter identified as the patients' response to treatment. Median follow-up times for the tumor volume after SBRT were 126 days. These results have proven the use of mathematical modeling in preclinical anticancer investigations as a potential prognostic tool