Modeling Urinary Dysfunction After External Beam Radiation Therapy of the Prostate Using Bladder Dose-Surface Maps: Evidence of Spatially Variable Response of the Bladder Surface

Yahya, Noorazrul; Ebert, Martin A.; House, Michael J.; Kennedy, Angel; Matthews, J. N. S.; Joseph, David; Denham, James W.

doi:10.1016/j.ijrobp.2016.10.024

Cited by 42 publications

(79 citation statements)

References 34 publications

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“…[31]) and this may affect the results in "blurring" the dose/volume-relationship. An interesting field of investigation would be the integration of the weight of non-dosimetric factors into DSMs-based analyses which has rarely been reported [41,42].…”

Section: Discussionmentioning

confidence: 99%

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

et al. 2019

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The aim of this work was to determine how the spatial pattern of dose in the ano-rectal wall is related to late gastro-intestinal toxicity for prostate cancer patients treated with mainly IMRT. Patients and methods: Patients from the DUE-01 multicentre study with patient-reported (prospective) follow-up and available dosimetric data were included. Conventionally fractionated patients received 74-80 Gy and hypofractionated patients received 65-75.2 Gy. A large majority of the patients were treated with intensity-modulated radiotherapy (IMRT). Dose-surface maps (DSMs) for the anal canal and rectum as a single structure, and for the anal canal and the rectum separately, were co-registered rigidly in two dimensions and, for the patients with and without toxicity, respectively, the mean value of the dose in each pixel was calculated. A pixel-wise t-test was used to highlight the anatomical areas where there was a significant difference between the 'mean dose maps' of each group. Univariate models were also fitted to a range of spatial parameters. The endpoints considered were a mean grade !1 late fecal incontinence and a maximum grade !2 late rectal bleeding. Results: Twenty-six out of 213 patients had fecal incontinence, while 21/225 patients had rectal bleeding. Incontinence was associated with a higher dose in the caudal region of the anal canal; the most relevant spatial parameter was the lateral extent of the low and medium isodoses (5-49 Gy in EQD2). Bleeding was associated with high isodoses reaching the posterior rectal wall. The spatial dose parameters with the highest AUC value (.69) were the lateral extent of the 60-70 Gy isodoses. Conclusions: To avoid fecal incontinence it is important to limit the portion of the anal canal irradiated. Our analysis confirms that rectal bleeding is a function of similar spatial dose parameters for patients treated with IMRT, compared to previous studies on patients treated with three-dimensional conformal radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

et al. 2019

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“…In order to improve our understanding of the mechanisms underlying radiation-induced skin damage, future direction of the research is the inclusion of spatial information of dose distributions within the analysis of skin toxicity, as already performed for different toxicity endpoints after RT (46)(47)(48)(49)(50). The extraction of organ Dose-Surface Maps (51, 52) may allow for an enhanced prediction of RT toxicity based on the knowledge of the most radiosensitive skin areas.…”

Section: Discussionmentioning

confidence: 99%

NTCP Models for Severe Radiation Induced Dermatitis After IMRT or Proton Therapy for Thoracic Cancer Patients

et al. 2020

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Radiation therapy (RT) of thoracic cancers may cause severe radiation dermatitis (RD), which impacts on the quality of a patient's life. Aim of this study was to analyze the incidence of acute RD and develop normal tissue complication probability (NTCP) models for severe RD in thoracic cancer patients treated with Intensity-Modulated RT (IMRT) or Passive Scattering Proton Therapy (PSPT). We analyzed 166 Non-Small-Cell Lung Cancer (NSCLC) patients prospectively treated at a single institution with IMRT (103 patients) or PSPT (63 patients). All patients were treated to a prescribed dose of 60 to 74 Gy in conventional daily fractionation with concurrent chemotherapy. RD was scored according to CTCAE v3 scoring system. For each patient, the epidermis structure (skin) was automatically defined by an in house developed segmentation algorithm. The absolute dose-surface histogram (DSH) of the skin were extracted and normalized using the Body Surface Area (BSA) index as scaling factor. Patient and treatment-related characteristics were analyzed. The Lyman-Kutcher-Burman (LKB) NTCP model recast for DSH and the multivariable logistic model were adopted. Models were internally validated by Leave-One-Out method. Model performance was evaluated by the area under the receiver operator characteristic curve, and calibration plot parameters. Fifteen of 166 (9%) patients developed severe dermatitis (grade 3). RT technique did not impact RD incidence. Total gross tumor volume (GTV) size was the only non dosimetric variable significantly correlated with severe RD (p = 0.027). Multivariable logistic modeling resulted in a single variable model including S 20Gy , the relative skin surface receiving more than 20 Gy (OR = 31.4). The cut off for S 20Gy was 1.1% of the BSA. LKB model parameters were TD 50 = 9.5 Gy, m = 0.24, n = 0.62. Both NTCP models showed comparably high prediction and calibration performances. Despite skin toxicity has long been considered a potential limiting factor in the clinical use of PSPT, no significant differences in RD incidence was found between RT modalities. Once externally validated, the availability of NTCP models for prediction of severe RD may advance treatment planning optimization.

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“…Several published results (26,27,31,35,36,73) converged in the identification of the trigone dose as strongly associated with worsening of symptoms and an increased risk of severe acute and late injury. The exact mechanisms controlling the trigone are still unclear; however, as this muscle is actively involved in sphincter opening, it is realistic to claim that its damage might elicit frequency, urgency and/or incontinence symptoms.…”

Section: Are There Exceptionally Sensitive and Critical Substructuresmentioning

confidence: 94%

“…Some studies from the literature underlined the need to overcome the assumption that the urinary bladder is uniformly sensitive to radiation (26,27,31,35,36,73). As a matter of fact, the bladder comprises several substructures which may have distinct radiobiological behaviors and sensitivities, leading to different impacts on distinct urinary symptoms (see Fig.…”

Section: Are There Exceptionally Sensitive and Critical Substructuresmentioning

confidence: 99%

Understanding Urinary Toxicity after Radiotherapy for Prostate Cancer: First Steps Forward

Rancati

Palorini

Cozzarini

et al. 2017

Tumori

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Tumori 2017; 103(5): [395][396][397][398][399][400][401][402][403][404] REVIEW -BONADONNA LECTURE SERIES may be differently related to the absorbed dose. For example, rectal bleeding arises as a serial effect and is mainly related to the absorption of high doses in small rectal mucosa volumes, whilst fecal incontinence is related to intermediate doses absorbed by large rectal volumes.The development of reliable models of radiation-induced toxicities along with the available level of technology has determined an efficient improvement of the treatment plans, even in dose-escalated or hypofractionated regimens. This is particularly true for moderate and severe rectal toxicities, which had an incidence close to 20% in the 1990s while in the most recent publications they have fallen below 7%-10%.However, an analogous result has not yet been reached in urinary symptoms. This is mainly due to the difficulty in sparing the bladder, which is partially but unavoidably included in the target volume, as well as to the clear lack of knowledge concerning the predictors of urinary toxicity. The main reason for this deficiency is probably the difficulty in following for a sufficiently long time a large number of patients whose clinical and dosimetry data need to be individually and prospectively collected with proper evaluation of urinary symptoms. Some important symptoms (e.g., incontinence) may indeed continuously arise after radiation therapy and their incidence reaches a plateau only many years (typically 5-8) after treatment. The fulfilment of reliable models of radiation-induced urinary sequelae is therefore made particularly challenging by the complexity of symptoms, their evolution over time, and the strong dependence on the baseline situation.It is widely acknowledged that radiation-induced toxicity is a multifactorial problem, depending not only on the delivered

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Modeling Urinary Dysfunction After External Beam Radiation Therapy of the Prostate Using Bladder Dose-Surface Maps: Evidence of Spatially Variable Response of the Bladder Surface

Abstract: A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.

Cited by 42 publications

References 34 publications

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

NTCP Models for Severe Radiation Induced Dermatitis After IMRT or Proton Therapy for Thoracic Cancer Patients

Understanding Urinary Toxicity after Radiotherapy for Prostate Cancer: First Steps Forward

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