Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

Authors: Panayiotis Mavroidis, Kevin A. Pearlstein, John Dooley, Jasmine Sun, Srinivas Saripalli, Shiva K. Das, Andrew Z. Wang, Ronald C. Chen

Published in: Radiation Oncology | Issue 1/2018

Login to get access

Abstract

Background

To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.

Methods

Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.

Results

For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.

Conclusions

Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.
Literature
1.
Fiorino C, Valdagni R, Rancati T, et al. Dose–volume effects for normal tissues in external radiotherapy: pelvis. Radiother Oncol. 2009;93:153–67.CrossRefPubMed
2.
Budaus L, Bolla M, Bossi A, et al. Functional outcome and complications following radiation therapy for prostate cancer: a critical analysis of the literature. Eur Urol. 2012;61:112–27.CrossRefPubMed
3.
Viswanathan AN, Yorke ED, Marks LB, et al. Radiation dose volume effects of the urinary bladder. Int J Radiat Oncol Biol. 2010;76:S123–9.CrossRef
4.
5.
Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.CrossRefPubMed
6.
Clark JA, Talcott JA. Symptom indexes to assess outcomes of treatment for early prostate cancer. Med Care. 2001;39:1118–30.CrossRefPubMed
7.
Chen RC, Basak R, Meyer AM, et al. Association between choice of radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance and patient-reported quality of life among men with localized prostate cancer. JAMA. 2017;317:1141–50.CrossRefPubMed
8.
Wagner LI, Wenzel L, Shaw E, et al. Patient-reported outcomes in phase II cancer clinical trials: lessons learned and future directions. J Clin Oncol. 2007;25:5058–62.CrossRefPubMed
9.
Chen RC, Mamon HJ, Chen YH, et al. Patient-reported acute gastrointestinal symptoms during concurrent chemoradiation treatment for rectal cancer. Cancer. 2010;116:1879–86.CrossRefPubMed
10.
Flores LT, Bennett AV, Law EB, et al. Patient-reported outcomes vs. clinician symptom reporting during Chemoradiation for rectal cancer. Gastrointest Cancer Res. 2012;5:119–24.PubMedPubMedCentral
11.
Chen RC, Zhang Y, Chen MH, et al. Patient-reported quality of life during radiation treatment for localized prostate cancer: results from a prospective phase II trial. BJU Int. 2012;110:1690–5.CrossRefPubMed
12.
Talcott J, Clark J, Manola J, et al. Bringing prostate cancer quality of life research back to the bedside: translating numbers into a format that patients can understand. J Urol. 2006;176:1558–63.CrossRefPubMed
13.
Matzinger O, Duclos F, van den Bergh A, et al. Acute toxicity of curative radiotherapy for intermediate- and high-risk localised prostate cancer in the EORTC trial 22991. Eur J Cancer. 2009;45:2825–34.CrossRefPubMed
14.
Mavroidis P, Price A, Fried D, et al. Dose-volume toxicity modeling for de-intensified chemo-radiation therapy for HPV-positive oropharynx cancer. Radiother Oncol. 2017;124:240–7.CrossRefPubMed
15.
Fowler JF. Brief summary of radiobiological principles in fractionated radiotherapy. Semin Radiat Oncol. 1992;2:16–21.CrossRef
16.
Fowler JF. Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys. 2009;73:1532–7.CrossRefPubMed
17.
Niemierko A. A generalized concept of equivalent uniform dose. Med Phys. 1999;26:1100.
18.
Kwa S, Lebesque J, Theuws JC, et al. Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys. 1998;42:1–9.CrossRefPubMed
19.
Seppenwoolde Y, Lebesque J, Jaeger K, et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2003;55:724–35.CrossRefPubMed
20.
Jackson A, Ten Haken RK, Robertson JM, et al. Analysis of clinical complication data for radiation hepatitis using a parallel architecture model. Int J Radiat Oncol Biol Phys. 1995;31:883–91.CrossRefPubMed
21.
Lind BK, Mavroidis P, Hyödynmaa S, et al. Optimization of the dose level for a given treatment plan to maximize the complication free tumor cure. Acta Oncol. 1999;38:787–98.CrossRefPubMed
22.
Källman P, Ågren AK, Brahme A. Tumor and normal tissue responses to fractionated non uniform dose delivery. Int J Radiat Biol. 1992;62:249–62.CrossRefPubMed
23.
Mavroidis P, Laurell G, Kraepelien T, et al. Determination and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy. Acta Oncol. 2003;42:865–81.CrossRefPubMed
24.
Herring DF. Methods for extracting dose-response curves from radiation therapy data, I: a unified approach. Int J Radiat Oncol Biol Phys. 1980;6:225–32.CrossRefPubMed
25.
Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716–23.CrossRef
26.
Wang K, Eblan MJ, Deal AM, et al. Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol. 2017;35:1387–94.CrossRefPubMed
27.
De Meerleer G, Vakaet L, Meersschout S, et al. Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients. Int J Radiat Oncol Biol Phys. 2004;60:777–87.CrossRefPubMed
28.
Guerrero Urbano T, Khoo V, Staffurth J, et al. Intensity-modulated radiotherapy allows escalation of the radiation dose to the pelvic lymph nodes in patients with locally advanced prostate cancer: preliminary results of a phase I dose escalation study. Clin Oncol. 2010;22:236–44.CrossRef
29.
Muller AC, Lutjens J, Alber M, et al. Toxicity and outcome of pelvic IMRT for node-positive prostate cancer. Strahlenther Onkol. 2012;188:982–9.CrossRefPubMed
30.
Goldner G, Wachter-Gerstner N, Wachter S, et al. Acute side effects during 3-D-planned conformal radiotherapy of prostate cancer. Differences between patient's self-reported questionnaire and the corresponding doctor's report. Strahlenther Onkol. 2003;179:320–7.CrossRefPubMed
31.
Stephens RJ, Hopwood P, Girling DJ, et al. Randomized trials with quality of life endpoints: are doctors' ratings of patients' physical symptoms interchangeable with patients' self-ratings? Qual Life Res. 1997;6:225–36.CrossRefPubMed
32.
Clauser SB, Ganz PA, Lipscomb J, et al. Patient-reported outcomes assessment in cancer trials: evaluating and enhancing the payoff to decision making. J Clin Oncol. 2007;25:5049–50.CrossRefPubMed
33.
Carillo V, Cozzarini C, Rancati T, et al. Relationships between bladder dose–volume/surface histograms and acute urinary toxicity after radiotherapy for prostate cancer. Radiother Oncol. 2014;111:100–5.CrossRefPubMed
34.
Chua B, Min M, Wood M, et al. Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes. J Med Imaging Radiat Oncol. 2013;57:482–9.CrossRefPubMed
35.
Myrehaug S, Chan G, Craig T, et al. A treatment planning and acute toxicity comparison of two pelvic nodal volume delineation techniques and delivery comparison of intensity-modulated radiotherapy versus volumetric modulated arc therapy for hypofractionated high-risk prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82:e657–62.CrossRefPubMed
36.
Vesprini D, Catton C, Jacks L, et al. Inverse relationship between biochemical outcome and acute toxicity after image-guided radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2012;83:608–16.CrossRefPubMed
37.
Gill S, Thomas J, Fox C, et al. Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Radiat Oncol. 2011;6:145.CrossRefPubMedPubMedCentral
38.
Tsai HK, Manola J, Abner A, et al. Patient-reported acute gastrointestinal toxicity in men receiving 3-dimensional conformal radiation therapy for prostate cancer with or without neoadjuvant androgen suppression therapy. Urol Oncol. 2005;23:230–7.CrossRefPubMed
39.
Zhu J, Simon A, Haigron P, et al. The benefit of using bladder sub-volume equivalent uniform dose constraints in prostate intensity-modulated radiotherapy planning. Onco Targets Ther. 2016;9:7537–44.CrossRefPubMedPubMedCentral
40.
Mavroidis P, Komisopoulos G, Buckey C, et al. Radiobiological evaluation of prostate cancer IMRT and conformal-RT plans using different treatment protocols. Phys Med. 2017;40:33–41.CrossRefPubMed
41.
Ågren AK: Quantification of the response of heterogeneous tumors and organized normal tissues to fractionated radiotherapy. Ph.D. Thesis. Stockholm: Stockholm University, 1995.
42.
Burman C, Kutcher GJ, Emami B, et al. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys. 1991;21:123–35.CrossRefPubMed
43.
Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.CrossRefPubMed
44.
Thor M, Olsson C, Oh JH, et al. Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy. Radiother Oncol. 2016;119:117–22.CrossRefPubMedPubMedCentral
45.
Cozzarini C, Rancati T, Carillo V, et al. Multi-variable models predicting specific patient-reported acute urinary symptoms after radiotherapy for prostate cancer: results of a cohort study. Radiother Oncol. 2015;116:185–91.CrossRefPubMed
46.
Palorini F, Rancati T, Cozzarini C, et al. Multi-variable models of large international prostate symptom score worsening at the end of therapy in prostate cancer radiotherapy. Radiother Oncol. 2016;118:92–8.CrossRefPubMed
47.
Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34:1402–18.CrossRefPubMedPubMedCentral
48.
Beetz I, Schilstra C, Van der Schaaf A, et al. NTCP models for patient-rated xerostomia and sticky saliva after treatment with intensity modulated radiotherapy for head and neck cancer: the role of dosimetric and clinical factors. Radiother Oncol. 2012;105:101–6.CrossRefPubMed
49.
Beetz I, Schilstra C, Van Luijk P, et al. External validation of three dimensional conformal radiotherapy based NTCP models for patient-rated xerostomia and sticky saliva among patients treated with intensity modulated radiotherapy. Radiother Oncol. 2012;105:94–100.CrossRefPubMed
Metadata
Title
Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy
Authors
Panayiotis Mavroidis
Kevin A. Pearlstein
John Dooley
Jasmine Sun
Srinivas Saripalli
Shiva K. Das
Andrew Z. Wang
Ronald C. Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-0961-x

Other articles of this Issue 1/2018

Radiation Oncology 1/2018 Go to the issue

Retraction Note

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

Letter to the Editor

In regard to “Tran A, Zhang J, Woods K, Yu V, Nguyen D, Gustafson G, Rosen L, Sheng K. Treatment planning comparison of IMPT, VMAT and 4π radiotherapy for prostate cases. Radiation oncology. 2017 Jan 11; 12(1):10”

Research

Early evaluation of radiation-induced parotid damage in patients with nasopharyngeal carcinoma by T2 mapping and mDIXON Quant imaging: initial findings

Research

Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity

Research

Radiation-induced parotid changes in oropharyngeal cancer patients: the role of early functional imaging and patient−/treatment-related factors

Research

Relation of baseline neutrophil-to-lymphocyte ratio to survival and toxicity in head and neck cancer patients treated with (chemo-) radiation