| 1. |
- Thor, M., et al.
(författare)
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Inter-institutional analysis demonstrates the importance of lower than previously anticipated dose regions to prevent late rectal bleeding following prostate radiotherapy
- 2018
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 127:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate whether inter-institutional cohort analysis uncovers more reliable dose-response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy. Material and methods: Data from five institutions were used. Rectal dose-volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70-86.4 Gy@1.8-2.0 Gy/fraction were obtained, and corrected for fractionation effects (alpha/beta = 3 Gy). Cohorts with best-fit Lyman-Kutcher-Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose-response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability. Results: Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer-Lemeshow p-value, p(HL) = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; p(HL) = 0.63), indicating a logistically shaped dose-response. Conclusion: We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose-volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy. (C) 2018 Elsevier B. V. All rights reserved. Radiotherapy and Oncology 127 (2018) 88-95
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| 2. |
- Oh, J. H., et al.
(författare)
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A Factor Analysis Approach for Clustering Patient Reported Outcomes
- 2016
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Ingår i: Methods of Information in Medicine. - : Georg Thieme Verlag KG. - 0026-1270 .- 2511-705X. ; 55:5, s. 431-439
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the field of radiation oncology, the use of extensive patient reported outcomes is increasingly common to measure adverse side effects after radiotherapy in cancer patients. Factor analysis has the potential to identify an optimal number of latent factors (i.e., symptom groups). However, the ultimate goal of treatment response modeling is to understand the relationship between treatment variables such as radiation dose and symptom groups resulting from FA. Hence, it is crucial to identify clinically more relevant symptom groups and improved response variables from those symptom groups for a quantitative analysis. Objectives: The goal of this study is to design a computational method for finding clinically relevant symptom groups from PROs and to test associations between symptom groups and radiation dose. Methods: We propose a novel approach where exploratory factor analysis is followed by confirmatory factor analysis to determine the relevant number of symptom groups. We also propose to use a combination of symptoms in a symptom group identified as a new response variable in linear regression analysis to investigate the relationship between the symptom group and dose-volume variables. Results: We analyzed patient-reported gastrointestinal symptom profiles from 3 datasets in prostate cancer patients treated with radiotherapy. The final structural model of each dataset was validated using the other two datasets and compared to four other existing FA methods. Our systematic EFA-CFA approach provided clinically more relevant solutions than other methods, resulting in new clinically relevant outcome variables that enabled a quantitative analysis. As a result, statistically significant correlations were found between some dose volume variables to relevant anatomic structures and symptom groups identified by FA. Conclusions: Our proposed method can aid in the process of understanding PROs and provide a basis for improving our understanding of radiation-induced side effects.
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| 3. |
- Thor, M, et al.
(författare)
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Temporal patterns of patient-reported trismus and associated mouth-opening distances in radiotherapy for head and neck cancer: A prospective cohort study.
- 2018
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Ingår i: Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. - : Wiley. - 1749-4486. ; 43:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- To identify temporal patterns of patient-reported trismus during the first year post-radiotherapy, and to study their associations with maximal interincisal opening distances (MIOs).Single institution case series.University hospital ENT clinic.One hundred and ninety-six subjects who received radiotherapy (RT) for head and neck cancer (HNC) with or without chemotherapy in 2007-2012 to a total dose of 64.6/68Gy in 38/34 fractions, respectively. All subjects were prospectively assessed for mouth-opening ability (Gothenburg Trismus Questionnaire (GTQ), European Organization for Research and Treatment of Cancer quality of life Questionnaire (EORTC QLQ-H&N35), and MIO) pre-RT and at 3, 6 and 12months after RT.Correlations between temporally robust GTQ symptoms and MIO as given by Pearson's correlation coefficients (Pr ); temporally robust GTQ-symptom domains as given by factor analysis; rates of trismus with respect to baseline by risk ratios (RRs).Four temporally robust domains were identified: Eating (3-7 symptoms), Jaw (3-7), Pain (2-5) and Quality of Life (QoL, 2-5), and included 2-3 persistent symptoms across all post-RT assessments. The median RR for a moderate/severe (>2/>3) cut-off was the highest for Jaw (3.7/3.6) and QoL (3.2/2.9). The median Pr between temporally robust symptoms and MIO post-radiotherapy was 0.25-0.35/0.34-0.43/0.24-0.31/0.34-0.50 for Eating/Jaw/Pain/QoL, respectively.Mouth-opening distances in patients with HNC post-RT can be understood in terms of associated patient-reported outcomes on trismus-related difficulties. Our data suggest that a reduction in MIO can be expected as patients communicate their mouth-opening status to interfere with private/social life, a clinical warning signal for emerging or worsening trismus as patients are being followed after RT.
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| 4. |
- Beasley, W., et al.
(författare)
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Image-based Data Mining to Probe Dosimetric Correlates of Radiation-induced Trismus
- 2018
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 102:4, s. 1330-1338
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To identify imaged regions in which dose is associated with radiation-induced trismus after head and neck cancer radiation therapy (HNRT) using a novel image-based data mining (IBDM) framework. Methods and Materials: A cohort of 86 HNRT patients were analyzed for region identification. Trismus was characterized as a continuous variable by the maximum incisor-to-incisor opening distance (MID) at 6 months after radiation therapy. Patient anatomies and dose distributions were spatially normalized to a common frame of reference using deformable image registration. IBDM was used to identify clusters of voxels associated with MID (P <= .05 based on permutation testing). The result was externally tested on a cohort of 35 patients with head and neck cancer. Internally, we also performed a dose-volume histogram-based analysis by comparing the magnitude of the correlation between MID and the mean dose for the IBDM-identified cluster in comparison with 5 delineated masticatory structures. Results: A single cluster was identified with the IBDM approach (P < .01), partially overlapping with the ipsilateral masseter. The dose-volume histogram-based analysis confirmed that the IBDM cluster had the strongest association with MID, followed by the ipsilateral masseter and the ipsilateral medial pterygoid (Spearman's rank correlation coefficients: R-s = -0.36, -0.35, -0.32; P = .001, .001, .002, respectively). External validation confirmed an association between mean dose to the IBDM cluster and MID (R-s = -0.45; P = .007). Conclusions: IBDM bypasses the common assumption that dose patterns within structures are unimportant. Our novel IBDM approach for continuous outcome variables successfully identified a cluster of voxels that are highly associated with trismus, overlapping partially with the ipsilateral masseter. Tests on an external validation cohort showed an even stronger correlation with trismus. These results support use of the region in HNRT treatment planning to potentially reduce trismus. (C) 2018 Elsevier Inc. All rights reserved.
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| 5. |
- Olsson, Caroline, 1970, et al.
(författare)
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A Systematic Post-QUANTEC Review of Tolerance Doses for Late Toxicity After Prostate Cancer Radiation Therapy
- 2018
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 102:5, s. 1514-1532
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thresholds, that is, statistically significant (P ≤.05) cutoff points between symptomatic and asymptomatic patients in a certain study. Methods and Materials: PubMed was scrutinized for full-text articles in English after QUANTEC (January 1, 2010). The inclusion criteria were randomized controlled trials, case-control studies, or cohort studies with tolerance doses for late distinct symptoms ≥3 months after primary radiation therapy for prostate cancer (N > 30). All DVH thresholds were converted into equivalent doses in 2-Gy fractions (EQD2α/β) and were fitted with a linear or linear-quadratic function (goodness of fit, R2). The review was registered on PROSPERO (CRD42016042464). Results: From 33 identified studies, which included 36 to 746 patients per symptom domain, the majority of dose/volume tolerances were derived for GI toxicity after EBRT alone (GI, 97 thresholds; GU, 8 thresholds; SD, 1 threshold). For 5 symptoms (defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding), relationships between dose/volume tolerances across studies (R2 = 0.93 [0.82-1.00]), and across symptoms, leading to a curve for overall GI toxicity (R2 = 0.98), could be determined. For these symptoms, mainly rectal thresholds were found throughout low and high doses (10 Gy ≤ equivalent dose in 2-Gy fractions using α/β = 3Gy (EQD23) ≤ 50 Gy and 55 Gy ≤ EQD23 ≤ 78 Gy, respectively). For BT with or without EBRT, dose/volume tolerances were also mainly identified for GI toxicity (GI, 14 thresholds; GU, 4 thresholds; SD, 2 thresholds) with the largest number of DVH thresholds concerning rectal bleeding (5 thresholds). Conclusions: Updated dose/volume tolerances after QUANTEC were found for 17 GI, GU, or SD symptoms. A DVH curve described the relationship between dose/volume tolerances across 5 GI symptoms after EBRT alone. Restricting treatments for EBRT alone using the lower boundaries of this curve is likely to limit overall GI toxicity, but this should be explored prospectively. Dose/volume tolerances for GU and SD toxicity after EBRT alone and after BT with or without EBRT were scarce and support further research including data-sharing initiatives to untangle the dose/volume relationships for these symptoms. © 2018 Elsevier Inc.
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| 6. |
- Olsson, Caroline, 1970, et al.
(författare)
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Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer.
- 2014
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Ingår i: Physics in medicine and biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 59:14, s. 3749-3759
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Tidskriftsartikel (refereegranskat)abstract
- When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.
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| 7. |
- Thorek, Daniel L J, et al.
(författare)
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Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models.
- 2015
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 93:2, s. 444-453
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry.
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