The Relation Between Tumour Lethal Doses and the Radiosensitivity of Tumour Cells

Munro, T.R.; Gilbert, C. W.

doi:10.1259/0007-1285-34-400-246

Cited by 230 publications

(88 citation statements)

References 12 publications

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“…The random killing of clonogens by irradiation is well described by Poisson statistics. ( 33 , 34 ) Using the linear quadratic expression for cell killing, we calculated TCP with the following formula:

TCP = e^{- N {(S F_{2})}^{\frac{D}{D_{r e f}} \cdot \frac{α / β + D / n}{α / β + D_{r e f}}}},

…”

Section: Methodsmentioning

confidence: 99%

Intensity modulated radiation therapy versus three‐dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison

MacDonald

Ahmad

Kachris

et al. 2007

J Applied Clin Med Phys

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The present study compared the dosimetry of intensity‐modulated radiation therapy (IMRT) and three‐dimensional conformal radiation therapy (3D‐CRT) techniques in patients treated for high‐grade glioma. A total of 20 patients underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion. Prescription dose and normal‐tissue constraints were identical for the 3D‐CRT and IMRT plans. The prescribed dose was 59.4 Gy delivered at 1.8 Gy per fraction using 4 – 10 MV photons. Normal‐tissue dose constraints were 50 – 54 Gy for the optic chiasm and nerves, and 55 – 60 Gy for the brainstem.The IMRT plan yielded superior target coverage as compared with the 3D‐CRT plan. Specifically, minimum and mean planning target volume cone down doses were 54.52 Gy and 61.74 Gy for IMRT and 50.56 Gy and 60.06 Gy for 3D‐CRT (p≤0.01). The IMRT plan reduced the percent volume of brainstem receiving a dose greater than 45 Gy by 31% (p=0.004) and the percent volume of brain receiving a dose greater than 18 Gy, 24 Gy, and 45 Gy by 10% (p=0.059), 14% (p=0.015), and 40% (p≤0.0001) respectively. With IMRT, the percent volume of optic chiasm receiving more than 45 Gy was also reduced by 30.40% (p=0.047). As compared with 3D‐CRT, IMRT significantly increased the tumor control probability (p≤0.005) and lowered the normal‐tissue complication probability for brain and brainstem (p<0.033).Intensity‐modulated radiation therapy improved target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while minimizing toxicity, therefore potentially improving outcomes in patients with high‐grade glioma.PACs number: 87.53 Tf

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TCP = e^{- N {(S F_{2})}^{\frac{D}{D_{r e f}} \cdot \frac{α / β + D / n}{α / β + D_{r e f}}}},

…”

Section: Methodsmentioning

confidence: 99%

Intensity modulated radiation therapy versus three‐dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison

MacDonald

Ahmad

Kachris

et al. 2007

J Applied Clin Med Phys

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“…Considering the entire PTV and a sensitivity level of 50% we find that SB90-70 shows a relative loss in expected overall TCP of 5.10%, SB80-74 shows a relative loss in expected TCP of 5.65 %, SB91-81 shows a relative loss in expected TCP of 3.78 %, and risk-adaptive optimization shows a relative loss in expected overall TCP of only 0.84 %, when compared to the expected overall TCP at a sensitivity level of 100%. While these relative loses in overall expected TCP appear to be modest it should be noted that tumors are the ultimate parallel structures, and therefore a tumor is controlled if, and only if, all tumor subvolumes are controlled [32]. Thus, the highest risk tumor subvolume having the lowest TCP will drive the expected local control (cf.…”

Section: The Impact Of Sensitivity Loss On Local Tumor Controlmentioning

confidence: 99%

On the impact of functional imaging accuracy on selective boosting IMRT

Kim

2009

Physica Medica

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In order to quantify the impact of loss of functional imaging sensitivity and specificity on tumor control and normal tissue toxicity for selective boosting IMRT four selective boosting scenarios were designed: SB91-81 (EUD=91Gy for the high risk tumor subvolume and EUD=81Gy for a remaining low risk PTV (rPTV)), SB80-74, SB90-70, and risk-adaptive optimization. For each sensitivity loss level the loss in tumor control probability (ΔTCP) was calculated. For each specificity loss level, the increase in rectal and the bladder toxicity was quantified using the radiobiological indices (equivalent uniform dose (EUD) and normal tissue complication probability (NTCP)) and %-volumes irradiated.The impact of loss in sensitivity on local tumor control was maximal when the prescription dose level for rPTV had the lowest value. The SB90-70 plan had a ΔTCP= 29.6%, the SB91-81 plan had a ΔTCP = 9.5%, while for risk-adaptive optimization a ΔTCP= 4.7% was found. Independent of planning technique loss in functional imaging specificity appears to have a minimal impact on the expected normal tissue toxicity, since an increase in rectal or bladder toxicity as a function of loss in specificity was not observed. Additionally, all plans fulfilled the rectum and the bladder sparing criteria found in the literature for late rectal bleeding and genitourinary complications.Our study shows that the choice of a low-risk classification for the rPTV in selective boosting IMRT may lead to a significant loss in TCP. Furthermore, for the example considered in which normal tissue complications can be limited through the use of a tissue expander it appears that the therapeutic ratio can be improved using a functional imaging technique with a high sensitivity and limited specificity. While for cases were this is not possible an optimal balance between sensitivity and specificity has to be found.

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“…Since tumors are the ultimate parallel structures, the overall tumor is controlled if and only if all of the tumor subvolumes are controlled, i.e. if every single potentially malignant cell is damaged to such an extent that it cannot continue to proliferate [15]. In what follows, let us now assume that we have in subvolume j an inhomogeneous dose distribution, where is the fractional volume of subvolume j receiving the constant total dose, , then the expected TCP for subvolume j is given by (cf.…”

Section: Subvolume-based Tcp Modelmentioning

confidence: 99%

Risk-adaptive optimization: Selective boosting of high-risk tumor subvolumes

Kim

2006

International Journal of Radiation Oncology*Biology*Physics

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Background and purpose-A tumor subvolume-based, risk-adaptive optimization strategy is presented.Methods and materials-Risk-adaptive optimization employs a biological objective function instead of an objective function based on physical dose constraints. Using this biological objective function, TCP is maximized for different tumor risk regions while at the same time minimizing NTCP for organs at risk (OAR). The feasibility of risk-adaptive optimization was investigated for a variety of tumor subvolume geometries, risk-levels, and slopes of the TCP curve. Furthermore, the impact of a correlation parameter, δ, between TCP and NTCP on risk-adaptive optimization was investigated.Results-Employing risk-adaptive optimization, it is possible in a prostate cancer model to increase EUD by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing predicted normal tissue complications in organs at risk. For all tumor subvolume geometries investigated, we found that the EUD to high-risk tumor subvolumes could be increased significantly without increasing normal tissue complications above those expected from a treatment plan aiming for uniform dose coverage of the PTV. We furthermore found that the tumor subvolume with the highest risk classification had the largest influence on the design of the risk-adaptive dose distribution. The parameter δ had little effect on risk-adaptive optimization. However, the clinical parameters D 50 and γ 50 that represent the risk classification of subtumor volumes had the largest impact on risk-adaptive optimization.Conclusions-On the whole, risk-adaptive optimization yields heterogeneous dose distributions that match the risk level distribution of different subvolumes within the tumor volume.

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The Relation Between Tumour Lethal Doses and the Radiosensitivity of Tumour Cells

Cited by 230 publications

References 12 publications

Intensity modulated radiation therapy versus three‐dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison

Intensity modulated radiation therapy versus three‐dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison

On the impact of functional imaging accuracy on selective boosting IMRT

Risk-adaptive optimization: Selective boosting of high-risk tumor subvolumes

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