1,720,976 research outputs found

    Modelling the impact of fractionation on late urinary toxicity after postprostatectomy radiation therapy

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    Purpose To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor.Methods and Materials Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor Î3 (fixing α/Î2 = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population.Results The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/Î2 values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/Î2 = 5 Gy, best-fit values for Î3 were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for Î3 (0.6-1.0 Gy/d), with comparable goodness of fit for α/Î2 values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including Î3 were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC = 0.73).Conclusions The unexpected impact of moderate hypofractionation on severe incontinence and hematuria after postprostatectomy radiation therapy may be explained by a bladder α/Î2 value <1 Gy or, radiobiologically more plausible, by introducing a time factor likely to represent a previously hypothesized consequential component of late effect

    External validation of an 18F-FDG-PET radiomic model predicting survival after radiotherapy for oropharyngeal cancer

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    Purpose/objective The purpose of the study is to externally validate published 18F-FDG-PET radiomic models for outcome prediction in patients with oropharyngeal cancer treated with chemoradiotherapy. Material/methods Outcome data and pre-radiotherapy PET images of 100 oropharyngeal cancer patients (stage IV:78) treated with concomitant chemotherapy to 66–69 Gy/30 fr were available. Tumors were segmented using a previously validated semi-automatic method; 450 radiomic features (RF) were extracted according to IBSI (Image Biomarker Standardization Initiative) guidelines. Only one model for cancer-specific survival (CSS) prediction was suitable to be independently tested, according to our criteria. This model, in addition to HPV status, SUVmean and SUVmax, included two independent meta-factors (Fi), resulting from combining selected RF clusters. In a subgroup of 66 patients with complete HPV information, the global risk score R was computed considering the original coefficients and was tested by Cox regression as predictive of CSS. Independently, only the radiomic risk score RF derived from Fi was tested on the same subgroup to learn about the radiomics contribution to the model. The metabolic tumor volume (MTV) was also tested as a single predictor and its prediction performances were compared to the global and radiomic models. Finally, the validation of MTV and the radiomic score RF were also tested on the entire dataset. Results Regarding the analysis of the subgroup with HPV information, with a median follow-up of 41.6 months, seven patients died due to cancer. R was confirmed to be associated to CSS (p value = 0.05) with a C-index equal 0.75 (95% CI=0.62–0.85). The best cut-off value (equal to 0.15) showed high ability in patient stratification (p=0.01, HR=7.4, 95% CI=1.6–11.4). The 5-year CSS for R were 97% (95% CI: 93–100%) vs 74% (56–92%) for low- and high-risk groups, respectively. RF and MTV alone were also significantly associated to CSS for the subgroup with an almost identical C-index. According to best cut-off value (RF>0.12 and MTV>15.5cc), the 5-year CSS were 96% (95% CI: 89–100%) vs 65% (36–94%) and 97% (95% CI: 88–100%) vs 77% (58–93%) for RF and MTV, respectively. Results regarding RF and MTV were confirmed in the overall group. Conclusion A previously published PET radiomic model for CSS prediction was independently validated. Performances of the model were similar to the ones of using only the MTV, without improvement of prediction accuracy

    FDG-PET/CT Predicts Outcome in Oropharingeal Carcinoma Patients Undergoing Intensity Modulated Radiation Therapy with Dose Escalation to FDG-avid Tumour Volumes

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    Objective: To evaluate the predictive value of FDG-PET/CT parameters on outcome of oropharyngeal squamocellular cancer (OSCC) patients undergoing helical tomotherapy (HTT), with dose escalation to FDG-PET/CT positive tumour volumes using the simultaneous integrated boost (SIB) technique. Materials and Methods: We analysed 41 patients studied by FDG-PET/CT and treated with radical intent between 2005 and 2014 for OSCC. HTT-SIB was delivered in 30 fractions concomitantly: 69 Gy, as SIB, to the PET-positive volume (biological target volume - BTV-PET), both to the primary tumour (T) and lymph nodes (N), 66 Gy to the T and positive N, 54 Gy to the laterocervical nodes at risk. Selected PET parameters were recovered: maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) obtained with different thresholds (40-50-60% of the SUVmax) for T and N. The correlation between these parameters and the 3-year overall (OS), cancer specific (CSS), disease free (DFS), local relapse free for T and N (LRFS-T and LRFS-N) and distant metastasis free (DMFS) survivals was investigated. Results: The median follow-up was 37 months (range: 3-125). The 3-year OS, CSS, DFS, LRFST, LRFS-N and DMFS were 86%, 88%, 76%, 83%, 88% and 91%, respectively. BTVT+ N>30.9cc and BTV-T>22.4cc were correlated with CSS (p=0.02) and OS (p=0.006) respectively; TLG-T-60>34.6cc was correlated with CSS (p=0.04) and OS (p=0.01). MTV-T-60>4.4cc could predict a higher risk of relapse/death (CSS: p=0.033; hazard ratio (HR) =10.92; OS: p=0.01; HR=16.4; LRFS-T: p=0.02; HR=13.90; LRFS-T+N: p=0.03; HR=6.50). Conclusion: PET parameters predicted survival outcomes and may be considered in the future in the implementation of more personalized treatment schedules in patients affected by OSCC undergoing radiotherapy. FDG-PET/CT dose escalated HTT-SIB allowed very promising 3-year disease control rates in OSCC patients

    Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation

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    Purpose To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÃve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Material and methods Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n = 19; VMAT/Rapidarc n = 57; Tomotherapy n = 45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Results Significant differences (p &lt; 0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⤠0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR = 1.018) or late Grade2 lymphopenia (OR = 1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC = 0.73) and IL-V40+smoking (AUC = 0.904) for acute/late respectively. Conclusions Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT

    Selecting the Optimal Candidate for Adjuvant Radiotherapy After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis

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    Background: The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial. Objective: We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features. Design, setting, and participants: We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes. Outcome measurements and statistical analysis: Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors. Results and limitations: On multivariable analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p = 0.4). Conversely, in patients with a risk score >= 2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study. Conclusions: ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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