Modeling radiation pneumonitis of pulmonary stereotactic body radiotherapy: The impact of a local dose–effect relationship for lung perfusion loss

Selvaraj, J.; Lebesque, Joos V.; Hope, Andrew; Gückenberger, Matthias; Werner‐Wasik, Maria; Peulen, Heike M.U.; Giuliani, Meredith; Mantel, Frederick; Belderbos, J.; Grills, I.S.; Sonke, Jan‐Jakob

doi:10.1016/j.radonc.2018.12.015

Cited by 17 publications

(13 citation statements)

References 24 publications

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“…To calculate the NTCP for the lung, we followed the method developed by Selvaraj et al 19 who fit several models to radiation pneumonitis data from patients who received SBRT. The authors found that the Lyman-Kutcher-Burman model with a logistic local dose-effect relation for perfusion loss derived from singlephoton emission computed tomography imaging data provided 'modest improvement' over other models.…”

Section: Normal Tissue Complication Probabilitymentioning

confidence: 99%

Using FFF beams to improve the therapeutic ratio of lung SBRT

et al. 2020

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Aim: The aim of this study was to investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams. Materials and methods: We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients’ treatment plans into the Eclipse 13·6 treatment planning system, in which we configured the AAA dose calculation model using representative beam data for a TrueBeam accelerator operated in 6-MV FFF mode. We then created new treatment plans by replacing the conventional FF beams in the original plans with FFF beams. Results: The FFF plans had better target coverage than the original FF plans did. For the planning target volume, FFF plans significantly improved the D98, D95, D90, homogeneity index and uncomplicated tumour control probability. In most cases, the doses to organs at risk were lower in FFF plans. FFF plans significantly reduced the mean lung dose, V10, V20, V30, and normal tissue complication probability for the total lung and improved the dosimetric indices for the ipsilateral lung. For most patients, FFF beams achieved lower maximum doses to the oesophagus, heart and the spinal cord, and a lower chest wall V30. Conclusions: Compared with FF beams, FFF beams achieved lower doses to organs at risk, especially the lung, without compromising tumour coverage; in fact, FFF beams improved coverage in most cases. Thus, replacing FF beams with FFF beams can achieve a better therapeutic ratio.

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Section: Normal Tissue Complication Probabilitymentioning

confidence: 99%

Using FFF beams to improve the therapeutic ratio of lung SBRT

et al. 2020

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“…The model uses a normalized dose and a sigmoidal first order Hill curve formulation, which could be accommodated in the PKPD formulation of our model after some adequate transformation. The challenge to be addressed is that the model from [50] describes phenomenological effects at a different (mezo-)scale than our PKPD model proposed here.…”

Section: Discussionmentioning

confidence: 99%

“…The challenge for RT is to balance the high dose to targeted tumor and the lowest possible dose to organs at risk [49]. A local dose-effect model based on stretched exponential and power law is proposed in [50]. The model is successfully used to predict RP incidence in NSCLC treated with SBRT in patients.…”

Section: Discussionmentioning

confidence: 99%

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies

Ionescu

Ghita

Copot

et al. 2020

JCM

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This paper introduces a mathematical compartmental formulation of dose-effect synergy modelling for multiple therapies in non small cell lung cancer (NSCLC): antiangiogenic, immuno- and radiotherapy. The model formulates the dose-effect relationship in a unified context, with tumor proliferating rates and necrotic tissue volume progression as a function of therapy management profiles. The model accounts for inter- and intra-response variability by using surface model response terms. Slow acting peripheral compartments such as fat and muscle for drug distribution are not modelled. This minimal pharmacokinetic-pharmacodynamic (PKPD) model is evaluated with reported data in mice from literature. A systematic analysis is performed by varying only radiotherapy profiles, while antiangiogenesis and immunotherapy are fixed to their initial profiles. Three radiotherapy protocols are selected from literature: (1) a single dose 5 Gy once weekly; (2) a dose of 5 Gy × 3 days followed by a 2 Gy × 3 days after two weeks and (3) a dose of 5 Gy + 2 × 0.075 Gy followed after two weeks by a 2 Gy + 2 × 0.075 Gy dose. A reduction of 28% in tumor end-volume after 30 days was observed in Protocol 2 when compared to Protocol 1. No changes in end-volume were observed between Protocol 2 and Protocol 3, this in agreement with other literature studies. Additional analysis on drug interaction suggested that higher synergy among drugs affects up to three-fold the tumor volume (increased synergy leads to significantly lower growth ratio and lower total tumor volume). Similarly, changes in patient response indicated that increased drug resistance leads to lower reduction rates of tumor volumes, with end-volume increased up to 25–30%. In conclusion, the proposed minimal PKPD model has physiological value and can be used to study therapy management protocols and is an aiding tool in the clinical decision making process. Although developed with data from mice studies, the model is scalable to NSCLC patients.

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“…Proponents for MLD argue that regional lung function is compromised at any dose, with the underlying assumption that local injury is linearly dependent on dose [ 24 ]. Local dose-response for perfusion loss has been demonstrated in SBRT patients [ 25 ]. Studies of changes in regional lung perfusion as a function of conventional fractionated doses have shown that this dependence may follow a sigmoid relationship, with no loss of perfusion below 10-15 Gy and a plateau at about 55 Gy [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Dose-Volume Predictors of Radiation Pneumonitis After Lung Stereotactic Body Radiation Therapy (SBRT): Implications for Practice and Trial Design

Moiseenko¹,

Grimm²,

Yorke³

et al. 2020

Cureus

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Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD) <8 Gy and normal lung receiving at least 20 Gy, V 20Gy <10-15% to avoid lung toxicity. Support for preferred use of a particular dosimetric parameter has been limited. We performed a detailed dose-volume analysis of data on radiation pneumonitis (RP) following lung stereotactic body radiation therapy (SBRT) to search for parameters showing the strongest correlation with RP. Materials and methods Two patient cohorts (primary and metastatic lung tumor patients) from previously reported studies were analyzed. Total number of patients was 96, and incidence of grade ≥2 RP was 13.5% (13/96). Fitting to the logistic function was performed to investigate correlation between incidence of RP and reported dosimetric and volumetric parameters. Another independent cohort was used to explore correlation between dosimetric parameters. Results Among normal lung parameters (MLD and reported V x ), only MLD consistently showed significant correlation with incidence of RP. Gross tumor volume (GTV), internal target volume, planning target volume (PTV), and minimum dose covering 95% of GTV or PTV did not show statistical significance. A significant correlation between reported V x and MLD was observed in all cohorts. Conclusions In considering tumor- and target-specific (e.g., GTV, PTV) and normal lung-specific (e.g., MLD, V x ) metrics, MLD was the only parameter that consistently correlated with incidence of RP across both cohorts. Because SBRT planning constraints allow small normal lung volumes to receive high doses, utility of MLD is not obvious. The parallel structure of lung is one possible explanation, but correlation between dosimetric parameters obscures elucidation of the preferred or mechanistically based parameter to guide radiotherapy planning.

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Modeling radiation pneumonitis of pulmonary stereotactic body radiotherapy: The impact of a local dose–effect relationship for lung perfusion loss

Cited by 17 publications

References 24 publications

Using FFF beams to improve the therapeutic ratio of lung SBRT

Using FFF beams to improve the therapeutic ratio of lung SBRT

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies

Dose-Volume Predictors of Radiation Pneumonitis After Lung Stereotactic Body Radiation Therapy (SBRT): Implications for Practice and Trial Design

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