Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population

A. Cicchetti, T. Rancati, Martin Ebert, C. Fiorino, F. Palorini, A. Kennedy, D.J. Joseph, J.W. Denham, V. Vavassori, G. Fellin, B. Avuzzi, C. Stucchi, R. Valdagni

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    Abstract

    © 2016 Associazione Italiana di Fisica MedicaAim To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials Population included 1336 patients, 3-year minimum follow-up, treated with 66–80 Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ?2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. Results 4% of patients (45/1122) reported mean stool frequency grade >1; grade ?2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30–50 Gy) for both endpoints. EUDs calculated with n = 1 (OR = 1.04) and n = 0.35 (OR = 1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR = 1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR = 4.2) for rectal pain. Conclusion Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.
    Original languageEnglish
    Pages (from-to)1690-1697
    JournalPhysica Medica
    Volume32
    Issue number12
    DOIs
    Publication statusPublished - Dec 2016

    Fingerprint

    pain
    radiation therapy
    Prostatic Neoplasms
    Radiotherapy
    cancer
    Pain
    toxicity
    dosage
    grade
    Population
    Calibration
    Fecal Incontinence
    optimization
    logistics
    Cardiovascular Diseases
    Quality of Life
    predictions

    Cite this

    Cicchetti, A. ; Rancati, T. ; Ebert, Martin ; Fiorino, C. ; Palorini, F. ; Kennedy, A. ; Joseph, D.J. ; Denham, J.W. ; Vavassori, V. ; Fellin, G. ; Avuzzi, B. ; Stucchi, C. ; Valdagni, R. / Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population. In: Physica Medica. 2016 ; Vol. 32, No. 12. pp. 1690-1697.
    @article{d78638d08aec4d948b46fa212b77abae,
    title = "Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population",
    abstract = "{\circledC} 2016 Associazione Italiana di Fisica MedicaAim To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials Population included 1336 patients, 3-year minimum follow-up, treated with 66–80 Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ?2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. Results 4{\%} of patients (45/1122) reported mean stool frequency grade >1; grade ?2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1{\%}): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30–50 Gy) for both endpoints. EUDs calculated with n = 1 (OR = 1.04) and n = 0.35 (OR = 1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR = 1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR = 4.2) for rectal pain. Conclusion Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.",
    author = "A. Cicchetti and T. Rancati and Martin Ebert and C. Fiorino and F. Palorini and A. Kennedy and D.J. Joseph and J.W. Denham and V. Vavassori and G. Fellin and B. Avuzzi and C. Stucchi and R. Valdagni",
    year = "2016",
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    Cicchetti, A, Rancati, T, Ebert, M, Fiorino, C, Palorini, F, Kennedy, A, Joseph, DJ, Denham, JW, Vavassori, V, Fellin, G, Avuzzi, B, Stucchi, C & Valdagni, R 2016, 'Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population' Physica Medica, vol. 32, no. 12, pp. 1690-1697. https://doi.org/10.1016/j.ejmp.2016.09.018

    Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population. / Cicchetti, A.; Rancati, T.; Ebert, Martin; Fiorino, C.; Palorini, F.; Kennedy, A.; Joseph, D.J.; Denham, J.W.; Vavassori, V.; Fellin, G.; Avuzzi, B.; Stucchi, C.; Valdagni, R.

    In: Physica Medica, Vol. 32, No. 12, 12.2016, p. 1690-1697.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population

    AU - Cicchetti, A.

    AU - Rancati, T.

    AU - Ebert, Martin

    AU - Fiorino, C.

    AU - Palorini, F.

    AU - Kennedy, A.

    AU - Joseph, D.J.

    AU - Denham, J.W.

    AU - Vavassori, V.

    AU - Fellin, G.

    AU - Avuzzi, B.

    AU - Stucchi, C.

    AU - Valdagni, R.

    PY - 2016/12

    Y1 - 2016/12

    N2 - © 2016 Associazione Italiana di Fisica MedicaAim To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials Population included 1336 patients, 3-year minimum follow-up, treated with 66–80 Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ?2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. Results 4% of patients (45/1122) reported mean stool frequency grade >1; grade ?2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30–50 Gy) for both endpoints. EUDs calculated with n = 1 (OR = 1.04) and n = 0.35 (OR = 1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR = 1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR = 4.2) for rectal pain. Conclusion Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

    AB - © 2016 Associazione Italiana di Fisica MedicaAim To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials Population included 1336 patients, 3-year minimum follow-up, treated with 66–80 Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ?2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. Results 4% of patients (45/1122) reported mean stool frequency grade >1; grade ?2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30–50 Gy) for both endpoints. EUDs calculated with n = 1 (OR = 1.04) and n = 0.35 (OR = 1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR = 1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR = 4.2) for rectal pain. Conclusion Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

    U2 - 10.1016/j.ejmp.2016.09.018

    DO - 10.1016/j.ejmp.2016.09.018

    M3 - Article

    VL - 32

    SP - 1690

    EP - 1697

    JO - Physica Medica

    JF - Physica Medica

    SN - 1120-1797

    IS - 12

    ER -