Grading-System-Dependent Volume Effects for Late Radiation-Induced Rectal Toxicity After Curative Radiotherapy for Prostate Cancer

Laan, Hans Paul van der; Bergh, A. van den; Schilstra, Cornelis; Vlasman, Renske; Meertens, H.; Langendijk, Johannes A.

doi:10.1016/j.ijrobp.2007.07.2363

Cited by 51 publications

(19 citation statements)

References 29 publications

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“…Restricting rectal volumes to receiving 75 Gy and 70 Gy below 5% and 25%, respectively, has been demonstrated to be predictive of a very low incidence of late rectal bleeding. 3,6,7,17,[29][30][31][32][33] These results were consistent, although different methods of defining the rectum have been used in these studies. This leads to the assumption that the rectum behaves as a serial-like organ when doses .70 Gy are applied and that the definition of the rectum as an OAR therefore plays a subordinate role.…”

Section: Discussionsupporting

confidence: 65%

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose–volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

Nitsche

Brannath

Brückner

et al. 2017

The British Journal of Radiology

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MN and RMH contributed to the conception, design, analysis and interpretation of data and helped with the final approval of the version to be published. MN, RMH and NT helped with the drafting of the article. WB and MB contributed to the statistics of the main study. DW contributed to the acquisition of data. AK contributed to the statistics of pre-study. NT helped with the planning and implementation of radiotherapy.Objective: The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dosevolume histogram (DVH) and rectal toxicity. Methods: In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves. Three definitions were identified to represent the most distinct differences in the shapes of the DVH curves: one anatomical definition recommended by the Radiation Therapy Oncology Group (RTOG) and two functional definitions based on the target volume. In the main study, the correlation between different relative DVH parameters derived from these three contouring definitions and the occurrence of rectal toxicity during and after EBRT was studied in two consecutive collectives. The first cohort consisted of 97 patients receiving primary curative EBRT and the second cohort consisted of 66 patients treated for biochemical recurrence after prostatectomy. Rectal toxicity was investigated by clinical investigation and scored according to the Common Terminology Criteria for Adverse Events. Candidate parameters were the volume of the rectum, mean dose, maximal dose, volume receiving at least 60 Gy (V 60 ), area under the DVH curve up to 25 Gy and area under the DVH curve up to 75 Gy in dependence of each chosen rectum definition. Multivariable logistic regression considered other clinical factors such as pelvine lymphatics vs local target volume, diabetes, prior rectal surgery, anticoagulation or haemorrhoids too.

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Section: Discussionsupporting

confidence: 65%

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose–volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

Nitsche

Brannath

Brückner

et al. 2017

The British Journal of Radiology

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“…Patient-derived toxicity grading was prospectively collected using CTC-AE v3.0 (3,17). Patients were asked to complete questionnaires concerning symptoms of rectal or bladder injury prior to and every week during radiotherapy as part of their standard care.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Cytokine Expression during IMRT for Prostate Cancer and Acute Treatment Toxicity

Christensen

Pintilie

Evans

et al. 2009

Clinical Cancer Research

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Purpose: Proteomic profiling of patients undergoing intensity-modulated radiotherapy (IMRT) for prostate cancer can identify unique biomarkers that reflect acute toxicity in normal tissues. Our objectives were to measure inflammatory cytokine proteins during IMRT and assess the variability of individual proteomic signatures. Experimental Design: Forty-two patients with intermediate-risk prostate cancer were recruited as follows: group 1, definitive IMRT (78 Gy in 39 fractions, n = 22), and group 2, IMRT postprostatectomy (66 Gy in 33 fractions, n = 20). Blood/urine samples were collected at baseline and weekly during IMRT. Acute toxicity was graded weekly during radiotherapy using CTC-AE v3.0 criteria. Multiplexed immunoassays were used to quantify cytokines including granulocyte macrophage colony-stimulating factor, IFN-γ, tumor necrosis factor-α, interleukin (IL)-1α, IL-2, IL6, IL-8, IL-10, and IL-12p70. Results: We observed positive correlations between cytokine expression between serum and plasma, but not between serum/plasma and urine. The Mann-Whitney test showed a significant increase in IFN-γ and IL-6 during IMRT (P = 0.0077, 0.0035). Increasing IL-2 and IL-1 expression were associated with increased probability of acute gastrointestinal and genitourinary toxicity, respectively. Conclusions: Determination of radiation-response signatures is feasible using multiplexed immunoassays and is a promising predictive early biomarker of toxicity outcomes. (Clin Cancer Res 2009;15(17):5576-83) Cellular damage caused by ionizing radiation induces specific proteins involved in DNA repair, cell death, inflammation, and other pathophysiologic responses (1). The majority of biomarker studies in radiation oncology have focused on predicting tumor response and survival (2). Clinically, the acute toxicity of prostate cancer radiotherapy manifest as gastrointestinal and genitourinary symptoms based on validated scoring criteria, [e.g., Common Terminology Criteria for Adverse Events (CTC-AE); ref. 3]. Radiotherapy dose escalation using intensity-modulated radiotherapy (IMRT) is associated with improved biochemical tumor control, yet still has radiation-induced toxicity. Dose-dependent markers of acute normal toxicity could help predict individuals at increased risk of radiotherapy-related injury and help to maximize the therapeutic ratio for individual patients.Rubin and colleagues were among the first to describe the role of cytokines (small glycoproteins involved in intercellular signaling) in mediating radiation toxicity (4). They showed in preclinical and clinical lung studies that levels of interleukin (IL)-1, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α were increased immediately after radiation exposure, and that chronically elevated TGF-β levels were associated with increased risk of pulmonary fibrosis. The link between radiation toxicity and cytokine expression is supported by studies showing that prolonged cytokine expression postradiotherapy is correlated to specific lung radi...

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“…This is particularly important for longer term studies in which it is known that one third of chronic gastrointestinal symptoms after pelvic radiotherapy are not related to the previous radiotherapy [7]. Also, symptoms are not always translated into the same grade of toxicity in different systems [34]. Rectal histology as a marker of toxicity is also potentially flawed because pelvic radiotherapy can cause gut injury at several points from the mid small bowel distally.…”

Section: Limitations To the Development Of Biomarkers For Normal Tissmentioning

confidence: 99%

Biomarkers of normal tissue toxicity after pelvic radiotherapy

Henson

Ang

2012

Current Opinion in Supportive &Amp; Palliative Care

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Biomarkers for gastrointestinal toxicity have a potential role in determining the outcomes of current and evolving radiotherapy techniques, identifying those patients at risk of greater degrees of toxicity to facilitate individualized treatment and determining whether symptoms that develop following treatment are related to the previous radiotherapy. Outcome measurement of pelvic radiotherapy has been plagued by inaccurate terminology and crude outcome measures. An accurate and acceptable biomarker or panel of biomarkers has the potential to revolutionize cancer management from treatment planning to posttreatment care. Several candidate biomarkers show promising results, but further robust research is required to clearly identify reliable biomarkers that can be translated into clinical practice.

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Grading-System-Dependent Volume Effects for Late Radiation-Induced Rectal Toxicity After Curative Radiotherapy for Prostate Cancer

Cited by 51 publications

References 29 publications

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose–volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose–volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

Longitudinal Cytokine Expression during IMRT for Prostate Cancer and Acute Treatment Toxicity

Biomarkers of normal tissue toxicity after pelvic radiotherapy

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