Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity

Balderson, Michael; Kirkby, Charles

doi:10.3109/09553002.2014.942014

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Increasing CTV maximum dose has resulted in higher EUDs and TCPs 21 22 Balderson et al 23 have also showed that large amount of target volume IHs is clinically acceptable. Considering our findings, the TCP values of target volume had just slightly lower values at lower priorities, but the NTCP values of bladder and rectum had lower values due to decreasing doses delivered to them.…”

Section: Discussionmentioning

confidence: 99%

Trade-off between the conflicting planning goals in correlation with patient’s anatomical parameters for intensity-modulated radiotherapy of prostate cancer patients

et al. 2019

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AimTo quantify the relationship between the planning target volume (PTV) dose homogeneity and organs at risk (OARs) sparing in correlation with anatomical parameters in prostate intensity-modulated radiotherapy (IMRT).Materials and methodsNine IMRT plans with various target dose constraints’ priorities were created for 15 prostate cancer patients. Selected PTV and OARs parameters were calculated for the patients. A trade-off was assessed between homogeneity index (HI) and OAR sparing. Several anatomical parameters were evaluated to investigate their effects on the OAR sparing and HI.ResultsInverse exponential relationships were found between the OAR sparing and HI (average R 2 of 0·983 and 0·994 for bladder and rectum, respectively). Decreasing the priority led to more OARs sparing (normal tissue complication probability reduction: 97·6 and 74·5%; mean dose reduction: 16·3 and 11·3% for bladder and rectum, respectively) and worsening of the HI (0·095–0·322) but with no significant effect on tumour control probability. Furthermore, OARs volumes, distances between OARs and PTV and their joint volumes had stronger correlations with OARs’ mean doses.ConclusionEnforcement of target dose constraints was more effective on the improvement of HIs for the patients with initial high HI values at low dose constraints’ priorities. Reducing the priority had more effects on the OARs sparing compared to HI, especially for the patients with high OAR doses in high priority plans. This can be attributed to smaller distances or greater joint volumes between the OARs and PTV.

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Section: Discussionmentioning

confidence: 99%

Trade-off between the conflicting planning goals in correlation with patient’s anatomical parameters for intensity-modulated radiotherapy of prostate cancer patients

et al. 2019

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“…Goitein came up with the idea that delivering higher dose to a portion of the target volume could increase TCP 7. Balderson et al 28. investigated heterogeneous doses through a prostate PTV with modeling work that incorporated a bystander effect model derived from in vitro experiments,29 and concluded that a large amount of dose heterogeneity (a standard deviation of 10 Gy about a mean of 78 Gy) through a prostate target volume could be clinically acceptable, and a moderate amount may even be optimal in terms of EUD and TCP.…”

Section: Discussionmentioning

confidence: 99%

A quantitative assessment of the consequences of allowing dose heterogeneity in prostate radiation therapy planning

Sun

Smith

Ghose

et al. 2018

J Applied Clin Med Phys

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Target dose uniformity has been historically an aim of volumetric modulated arc therapy (VMAT) planning. However, for some sites, this may not be strictly necessary and removing this constraint could theoretically improve organ‐at‐risk (OAR) sparing and tumor control probability (TCP). This study systematically investigates the consequences of PTV dose uniformity that results from the application or removal of an upper dose constraint (UDC) in the inverse planning process for prostate VMAT treatments. OAR sparing, target coverage, hotspots, and plan complexity were compared between prostate VMAT plans with and without the PTV UDC optimized using the progressive resolution optimizer (PRO, Varian Medical Systems, Palo Alto, CA). Removing the PTV UDC, the median D1cc reached 144.6% for the CTV and the PTV, and an average increase of 3.2% TCP was demonstrated, while CTV and PTV coverage evaluated by D99% was decreased by less than 0.6% with statistical significance. Moreover, systematic improvement in the rectum dose volume histograms was shown (a 5–10% decrease in the volume receiving 50% to 75% prescribed dose), resulting in an average decrease of 1.3% (P < 0.01) in the rectum normal tissue complication probability. Additional consequences included potentially increased dose to the urethra as evaluated by PTV D0.035cc (median: 153.4%), delivering 283 extra monitor units (MUs), and slightly higher degrees of modulation. In general, the results were consistent when a different optimizer (Photon Optimizer, Varian Medical Systems) was used. In conclusion, removing the PTV UDC is acceptable for localized prostate cases given the systematic improvement of rectal dose and TCP. It can be particularly useful for cases that do not meet the rectum dose constraints with the PTV UDC on. This comes with the foreseeable consequences of increased dose heterogeneity in the PTV and an increase in MUs and plan complexity. It also has a higher requirement for reproducing the position and size of the target and OARs during treatment. Finally, with the PTV UDC completely removed, in some cases the maximum doses within the PTV did approach levels that may be of concern for urethral toxicity and therefore in clinical implementation it may still be necessary to include a PTV UDC, but one based on limiting toxicity rather than enforcing dose homogeneity.

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“…Bystander effects have been shown in many different experiments, and these effects are well documented (Nagasawa and Little 1992, Prise and O'Sullivan 2009, Ebert et al 2010, Balderson and Kirkby 2014, Balderson and Kirkby 2015. Bystander effects seem to challenge the fundamental assumption of the prevalent LQ model (i.e.…”

Section: Bystander Effectsmentioning

confidence: 99%

The relative biological effectiveness of out-of-field dose

2015

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spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions.

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Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity

Cited by 7 publications

References 34 publications

Trade-off between the conflicting planning goals in correlation with patient’s anatomical parameters for intensity-modulated radiotherapy of prostate cancer patients

Trade-off between the conflicting planning goals in correlation with patient’s anatomical parameters for intensity-modulated radiotherapy of prostate cancer patients

A quantitative assessment of the consequences of allowing dose heterogeneity in prostate radiation therapy planning

The relative biological effectiveness of out-of-field dose

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