Dataset Information

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

ABSTRACT: Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r??=??0.98, P??

SUBMITTER: Denis-Bacelar AM

PROVIDER: S-EPMC5953197 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Denis-Bacelar Ana M AM Chittenden Sarah J SJ Murray Iain I Divoli Antigoni A Ralph McCready V V Dearnaley David P DP O'Sullivan Joe M JM Johnson Bernadette B Flux Glenn D GD

Physics in medicine and biology 20170401 7

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostat ...[more]

PMID: 28291739

Similar Datasets

Project description:BACKGROUND:Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. However, evidence from randomized, direct comparison of RT and SBRT is still lacking. METHODS/DESIGN:The PREST trial was designed as an interventional study without medicinal treatment. It is a phase 3, open-label, multicentric trial randomized 1:1. Inclusion criteria include painful spinal bone metastases presenting with a pain level?>?4 (or?>?1 if being treated with an analgesic) on the Numeric Rating Scale (NRS); expected intermediate/high prognosis (greater than 6?months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (<?7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy involving 4?Gy ×?5 fractions (fx) to the whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) involving 7?Gy ×?3 fx to the whole involved vertebra?+?10?Gy ×?3 fx on the macroscopic lesion (gross tumor volume (GTV)). In the experimental arm, the GTV will be contoured by registration with baseline MRI. DISCUSSION:The primary endpoint is overall pain reduction, defined in terms of variation between baseline and 3-month evaluation; pain will be measured using the NRS. Secondary endpoints include pain control duration; retreatment rates (after a minimum interval of 1?month); local control assessed with RECIST criteria; symptom progression free survival; progression-free survival; overall survival; and quality of life (at 0, 30, and 90?days). Accrual of 330 lesions is planned. The experimental arm is expected to have an improvement in overall pain response rates of 15% with respect to the standard arm (60% according to Chow et al. (Int J Radiat Oncol Biol Phys. 82(5):1730-7, 2012)). TRIAL REGISTRATION:ClinicalTrials.gov, NCT03597984 . Registered on July 2018.

Project description:ImportanceA survival prediction model for patients with bone metastases arising from lung cancer would be highly valuable.ObjectiveTo develop and validate a nomogram for assessing the survival probability of patients with metastatic lung cancer receiving radiotherapy for osseous metastases.Design, setting, participantsIn this prognostic study, the putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression analysis with backward elimination and model selection based on the Akaike information criterion. The nomogram was subjected to internal (bootstrap) and external validation; its calibration and discriminative ability were evaluated with calibration plots and the Uno C statistic, respectively. The training and validation set cohorts were from a tertiary medical center in northern Taiwan and a tertiary institution in southern Taiwan, respectively. The training set comprised 477 patients with metastatic lung cancer who received radiotherapy for osseous metastases between January 2000 and December 2013. The validation set comprised 235 similar patients treated between January 2011 and December 2017. Data analysis was conducted May 2018 to July 2018.Main outcomes and measuresThe nomogram end points were death within 3, 6, and 12 months.ResultsOf 477 patients in the training set, 292 patients (61.2%) were male, and the mean (SD) age was 62.86 (11.66) years. Of 235 patients in the validating set, 113 patients (48.1%) were male, and the mean (SD) age was 62.65 (11.49) years. In the training set, 186 (39%), 291 (61%), and 359 (75%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 4.21 (95% CI, 3.68-4.90) months. In the validating set, 84 (36%), 120 (51%), and 144 (61%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 5.20 (95% CI, 4.07-7.17) months. Body mass index (18.5 to <25 vs ≥25: hazard ratio [HR], 1.42; 95% CI, 1.14-1.78 and <18.5 vs ≥25: HR, 2.31; 95% CI, 1.56-3.44), histology (non-small cell vs small cell lung cancer: HR, 0.59; 95% CI, 0.41-0.86), epidermal growth factor receptor mutation (positive vs unknown: HR, 0.66; 95% CI, 0.46-0.93 and negative vs unknown: HR, 0.98; 95% CI, 0.66-1.45), smoking status (ever smoker vs never smoker: HR, 1.50; 95% CI, 1.24-1.83), age, and neutrophil to lymphocyte ratio were incorporated. The HRs of age and neutrophil to lymphocyte ratio were modeled nonlinearly with restricted cubic splines (both P < .001). The nomogram's discriminative ability was good in the training set (C statistic, ≥0.77; P < .001) and was validated using both an internal bootstrap method (C statistic, ≥0.76; P < .001) and an external validating set (C statistic, ≥0.75; P < .001). The calibration plots for the end points showed optimal agreement between the nomogram's assessment and actual observations.Conclusions and relevanceThe nomogram (with web-based tool) can be useful for assessing the probability of survival at 3, 6, and 12 months in patients with metastatic lung cancer referred for radiotherapy to treat bone metastases, and it may guide radiation oncologists in treatment decision making and engaging patients in end-of-life discussions and/or hospice referrals at appropriate times.

Project description:ImportanceProstate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site.ObjectiveTo evaluate the association of bone metastasis count and location with survival benefit from prostate RT.Design, setting, and participantsThis exploratory analysis of treatment outcomes based on metastatic site and extent as determined by conventional imaging (computed tomography/magnetic resonance imaging and bone scan) evaluated patients with newly diagnosed metastatic prostate cancer randomized within the STAMPEDE trial's metastasis M1 RT comparison. The association of baseline bone metastasis counts with overall survival (OS) and failure-free survival (FFS) was assessed using a multivariable fractional polynomial interaction procedure. Further analysis was conducted in subgroups.InterventionsPatients were randomized to receive either standard of care (androgen deprivation therapy with or without docetaxel) or standard of care and prostate RT.Main outcomes and measuresThe primary outcomes were OS and FFS.ResultsA total of 1939 of 2061 men were included (median [interquartile range] age, 68 [63-73] years); 1732 (89%) had bone metastases. Bone metastasis counts were associated with OS and FFS benefit from prostate RT. Survival benefit decreased continuously as the number of bone metastases increased, with benefit most pronounced up to 3 bone metastases. A plot of estimated treatment effect indicated that the upper 95% CI crossed the line of equivalence (hazard ratio [HR], 1) above 3 bone metastases without a detectable change point. Further analysis based on subgroups showed that the magnitude of benefit from the addition of prostate RT was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or 3 or fewer bone metastases without visceral metastasis (HR for OS, 0.62; 95% CI, 0.46-0.83; HR for FFS, 0.57; 95% CI, 0.47-0.70) than among patients with 4 or more bone metastases or any visceral/other metastasis (HR for OS, 1.08; 95% CI, 0.91-1.28; interaction P?=?.003; HR for FFS, 0.87; 95% CI, 0.76-0.99; interaction P?=?.002).Conclusions and relevanceIn this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with OS and FFS benefit from prostate RT in M1 disease.Trial registrationClinicalTrials.gov Identifier: NCT00268476; ISRCTN.com Identifier: ISRCTN78818544.

Dataset Information

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Publications

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets