International Journal of Radiation Oncology*Biology*Physics
Physics ContributionA Systematic Post-QUANTEC Review of Tolerance Doses for Late Toxicity After Prostate Cancer Radiation Therapy
Introduction
Over the past 3 decades, 2 major efforts have been conducted to better understand radiation therapy (RT) dose/volume tolerances for organs at risk (OARs) with the overall aim to limit the occurrence of severe late toxicity. The first consensus values were proposed in 1991.1 In 2010, the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) group presented evidence-based results made available from the accumulation of 3-dimensional (3D) treatment planning data.2 For prostate cancer, these efforts summarize dose/volume tolerances for OARs after external beam RT (EBRT) for commonly reported gastrointestinal (GI) and genitourinary (GU) toxicities and sexual dysfunction (SD).1, 3, 4, 5 However, dose/volume tolerances for distinct symptoms were typically not distinguished because these recommendations were based on toxicity scoring systems that combine symptoms (eg, by the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer6 and National Cancer Institute Common Terminology Criteria for Adverse Events7 systems). Furthermore, these QUANTEC reports on GI and GU toxicity and SD were derived for only the whole rectum, bladder, and penile bulb, respectively, and did not explicitly focus on dose/volume tolerances after treatments involving brachytherapy (BT).3, 4, 5
Since the publication of the 3 QUANTEC reports, dose/volume tolerances for late and distinct symptoms and other OARs have become available. The objective of this systematic review was to summarize dose/volume tolerances between distinct late GI and GU toxicities, SD symptoms, and relevant OARs after prostate cancer RT separately for EBRT alone and for BT with or without EBRT.
Section snippets
Search strategy
This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,8 and protocol details were registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016042464). The PubMed database was scrutinized for full-text articles in English published up to December 31, 2017, focusing on studies reporting dose/volume tolerances for late toxicities only after prostate cancer RT. For GI toxicity and SD after EBRT alone, the
Results
A total of 168 full-text articles were identified, of which 33 fulfilled the inclusion criteria. Of these 33 studies, 22 concerned EBRT alone (n = 6313 treated between 1993 and 2014) and 11 concerned BT with or without EBRT (n = 3836 treated between 1995 and 2010; Fig. 1; Table 1, Table 2, Table 3; Tables E1 and E2, available online at https://doi.org/10.1016/j.ijrobp.2018.08.015). All studies presented with at least “fair” study quality (mean score ± standard deviation, 6 ± 1). The studies
Discussion
This systematic review was based on dose/volume tolerances for late and distinct RT-induced toxicities after prostate cancer RT from 10,149 patients and 33 studies. We identified 97 dose/volume tolerances, 8 dose/volume tolerances, and 1 dose/volume tolerance as quantified by DVH thresholds for GI, GU, and SD toxicity, respectively, in 13 OARs after EBRT alone. The corresponding numbers after BT with or without EBRT were 14, 4, and 2 in 4 OARs. An overall GI toxicity DVH curve based on
Conclusions
This systematic review provides evidence in support of rectal dose/volume tolerances after prostate cancer EBRT alone for defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding within both the low- to intermediate-dose range (10 Gy ≤ EQD23 ≤ 50 Gy) and high-dose range (55 Gy ≤ EQD23 ≤ 78 Gy). The more sensitive symptom of defecation urgency implies that if its tolerance can be respected, the risk of development of other GI toxicities is low. Even though RT-induced
Acknowledgments
The authors acknowledge Konstantina Matsoukas at Memorial Sloan Kettering Cancer Center for conducting all initial literature searches. They thank all authors of individually published studies who clarified essential information on request.
References (58)
- et al.
Tolerance of normal tissue to therapeutic irradiation
Int J Radiat Oncol Biol Phys
(1991) - et al.
Radiation dose-volume effects in radiation-induced rectal injury
Int J Radiat Oncol Biol Phys
(2010) - et al.
Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)
Int J Radiat Oncol Biol Phys
(1995) - et al.
Bioeffect modeling and equieffective dose concepts in radiation oncology—terminology, quantities and units
Int J Radiat Oncol Biol Phys
(2012) - et al.
Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: Evidence from MRCRT01 trial ISRCTN 47772397
Int J Radiat Oncol Biol Phys
(2010) - et al.
Dose to the inferior rectum is strongly associated with patient reported bowel quality of life after radiation therapy for prostate cancer
Radiother Oncol
(2014) - et al.
Gastrointestinal dose-histogram effects in the context of dose-volume constrained prostate radiation therapy: Analysis of data from the RADAR prostate radiation therapy trial
Int J Radiat Oncol Biol Phys
(2015) - et al.
The dose–response of the anal sphincter region—An analysis of data from the MRC RT01 trial
Radiother Oncol
(2012) - et al.
Long term rectal function after high-dose prostate cancer radiotherapy: Results from a prospective cohort study
Radiother Oncol
(2014) - et al.
Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients
Radiother Oncol
(2016)
Dose/volume-response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions
Radiother Oncol
Functional data analysis in NTCP modeling: A new method to explore the radiation dose-volume effects
Int J Radiat Oncol Biol Phys
The benefits of including clinical factors in rectal normal tissue complication probability modeling after radiotherapy for prostate cancer
Int J Radiat Oncol Biol Phys
Identification of a rectal subregion highly predictive of rectal bleeding in prostate cancer IMRT
Radiother Oncol
Integrated models for the prediction of later genitourinary complaints after high-dose intensity modulated radiotherapy for prostate cancer: Making informed decisions
Radiother Oncol
Urinary symptoms following external beam radiotherapy of the prostate: Dose-symptom correlates with multiple-event and event-count models
Radiother Oncol
Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy
Radiother Oncol
Urinary obstruction in prostate cancer patients from the Dutch trial (68 Gy vs 78 Gy): Relationships with local dose, acute effects, and baseline characteristics
Int J Radiat Oncol Biol Phys
Radiation dose to the penile structures and patient-reported sexual dysfunction in long-term prostate cancer survivors
J Sex Med
Reduced radiation tolerance of penile structures associated with dose-escalated hypofractionated prostate radiotherapy
Urology
Dose-volume impact in high-dose-rate iridium-192 brachytherapy as a boost to external beam radiotherapy for localized prostate cancer—A phase II study
Radiother Oncol
Three-dimensional summation of rectal doses in brachytherapy combined with external beam radiotherapy for prostate cancer
Radiother Oncol
Defining the risk of developing grade 2 proctitis following 125I prostate brachytherapy using a rectal dose-volume histogram analysis
Int J Radiat Oncol Biol Phys
Severe rectal complications after prostate brachytherapy
Radiother Oncol
Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy
Brachytherapy
Urethral strictures following high-dose-rate brachytherapy for prostate cancer: Analysis of risk factors
Brachytherapy
Urethral pain among prostate cancer survivors 1 to 14 years after radiation therapy
Int J Radiat Oncol Biol Phys
A comparison of radiation dose to the bulb of the penis in men with and without prostate brachytherapy-induced erectile dysfunction
Int J Radiat Oncol Biol Phys
Localization of neurovascular bundles on pelvic CT and evaluation of radiation dose to structures putatively involved in erectile dysfunction after prostate brachytherapy
Int J Radiat Oncol Biol Phys
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Note—An online CME test for this article can be taken at https://academy.astro.org.
This research was funded in part through National Institutes of Health–National Cancer Institute Cancer Center Support Grant P30 CA008748 (M.T., A.J., and J.O.D.). Grants from the King Gustaf V Jubilee Clinic Cancer Foundation in Gothenburg, the Swedish Society for Medical Research, the Kamprad Family Foundation for Entrepreneurship Research & Charity, and the Research and Development Council of West Region County (Sweden) supported C.E.O.
Conflict of interest: none.