Limits...
Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer.

Cella L, D'Avino V, Liuzzi R, Conson M, Doria F, Faiella A, Loffredo F, Salvatore M, Pacelli R - Radiat Oncol (2013)

Bottom Line: Their median age was 73 years (range 53-85).At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events.This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biostructures and Bioimaging, National Council of Research (CNR), Naples, Italy. laura.cella@cnr.it.

ABSTRACT

Background: The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications.

Methods: A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53-85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman's rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC).

Results: At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69).

Conclusions: We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing previous acute toxicity and it is lower for patients who take AH/AC drugs. The developed NTCP model could represent a potentially useful tool to be used in prospective trial and for comparison among different RT techniques.

Show MeSH

Related in: MedlinePlus

Three-variable NTCP model curves as a function of V65 for patients who experienced gastro-intestinal (GI) acute toxicity (a) and for patients who did not (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3852304&req=5

Figure 2: Three-variable NTCP model curves as a function of V65 for patients who experienced gastro-intestinal (GI) acute toxicity (a) and for patients who did not (b).

Mentions: A three-variable model was suggested as the optimal order by bootstrap method. Figure 1b shows the five most frequently selected models within the bootstrapped subpopulations. The optimal model (model 1) includes V65, antihypertensive and/or anticoagulant (AH/AC) drugs use (yes = 1, no = 0) and previous acute toxicity (yes = 1, no = 0). The Spearman’s rank correlation coefficient of the model is 0.47 (p < 0.001) and the AUC of the corresponding ROC curve is 0.79. The best-fitted regression coefficients are given in Table 3. According to this model, the risk of late GI toxicity of grade G1 or G2 increases as V65 increases, it is higher for patients experiencing previous acute toxicity and it is lower for patients who take AH/AC drugs. Model 1 NTCP curves are represented in Figure 2a-b. In Table 3 the regression coefficients for the logistic model based on V65 only (model 2) are also reported. The Rs coefficient of model 2 is 0.28 (p < 0.001). The result of ROC analyses was a discrimination value for V65 of 29.3%.


Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer.

Cella L, D'Avino V, Liuzzi R, Conson M, Doria F, Faiella A, Loffredo F, Salvatore M, Pacelli R - Radiat Oncol (2013)

Three-variable NTCP model curves as a function of V65 for patients who experienced gastro-intestinal (GI) acute toxicity (a) and for patients who did not (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852304&req=5

Figure 2: Three-variable NTCP model curves as a function of V65 for patients who experienced gastro-intestinal (GI) acute toxicity (a) and for patients who did not (b).
Mentions: A three-variable model was suggested as the optimal order by bootstrap method. Figure 1b shows the five most frequently selected models within the bootstrapped subpopulations. The optimal model (model 1) includes V65, antihypertensive and/or anticoagulant (AH/AC) drugs use (yes = 1, no = 0) and previous acute toxicity (yes = 1, no = 0). The Spearman’s rank correlation coefficient of the model is 0.47 (p < 0.001) and the AUC of the corresponding ROC curve is 0.79. The best-fitted regression coefficients are given in Table 3. According to this model, the risk of late GI toxicity of grade G1 or G2 increases as V65 increases, it is higher for patients experiencing previous acute toxicity and it is lower for patients who take AH/AC drugs. Model 1 NTCP curves are represented in Figure 2a-b. In Table 3 the regression coefficients for the logistic model based on V65 only (model 2) are also reported. The Rs coefficient of model 2 is 0.28 (p < 0.001). The result of ROC analyses was a discrimination value for V65 of 29.3%.

Bottom Line: Their median age was 73 years (range 53-85).At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events.This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biostructures and Bioimaging, National Council of Research (CNR), Naples, Italy. laura.cella@cnr.it.

ABSTRACT

Background: The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications.

Methods: A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53-85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman's rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC).

Results: At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69).

Conclusions: We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing previous acute toxicity and it is lower for patients who take AH/AC drugs. The developed NTCP model could represent a potentially useful tool to be used in prospective trial and for comparison among different RT techniques.

Show MeSH
Related in: MedlinePlus