Abstract
Purpose
The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be ...adopted in the stereotactic treatment of early stage glottic cancer.
Methods and materials
Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated.
Results
For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test,
p
= 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489,
p
= 0.055), the displacement in the Y direction (r = 0.553,
p
= 0.026) and the subsequent margins to be adopted (r = 0.626,
p
= 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test
p
= 0.037 and
p
= 0.019, respectively).
Conclusions
In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.
Highlights • The predictive role of IVIM-DWI on cervical nodal response to chemo-radiotherapy was investigated. • Pre- and mid-treatment IVIM-DWI correlated significantly with the status of lymph ...nodes. • D values at baseline and at mid-RT had greater diagnostic accuracy than ADC values. • Perfusion-related parameters showed potential to further improve the predictive power.
Functional magnetic resonance imaging may provide several quantitative indices strictly related to distinctive tissue signatures with radiobiological relevance, such as tissue cellular density and ...vascular perfusion. The role of Intravoxel Incoherent Motion Diffusion Weighted Imaging (IVIM-DWI) and Dynamic Contrast-Enhanced (DCE) MRI in detecting/predicting radiation-induced volumetric changes of parotids both during and shortly after (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) was explored.
Patients with locally advanced oropharyngeal SCC were accrued within a prospective study offering both IVIM-DWI and DCE-MRI at baseline; IVIM-DWI was repeated at the 10th fraction of treatment. Apparent diffusion coefficient (ADC), tissue diffusion coefficient D
, perfusion fraction f and perfusion-related diffusion coefficient D
were estimated both at baseline and during RT. Semi-quantitative and quantitative parameters, including the transfer constant K
, were calculated from DCE-MRI. Parotids were contoured on T2-weighted images at baseline, 10th fraction and 8th weeks after treatment end and the percent change of parotid volume between baseline/10th fr (∆Vol
) and baseline/8th wk. (∆Vol
) computed. Correlations among volumetric changes and patient-, treatment- and imaging-related features were investigated at univariate analysis (Spearman's Rho).
Eighty parotids (40 patients) were analyzed. Percent changes were 18.2 ± 10.7% and 31.3 ± 15.8% for ∆Vol
and ∆Vol
, respectively. Among baseline characteristics, ∆Vol
was correlated to body mass index, patient weight as well as the initial parotid volume. A weak correlation was present between parotid shrinkage after the first 2 weeks of treatment and dosimetric variables, while no association was found after radiotherapy. Percent changes of both ADC and D
at the 10th fraction were also correlated to ∆Vol
. Significant relationships were found between ∆Vol
and baseline DCE-MRI parameters.
Both IVIM-DWI and DCE-MRI can help to detect/predict early (during treatment) and shortly after treatment completion the parotid shrinkage. They may contribute to clarify the correlations between volumetric changes of parotid glands and patient-/treatment-related variables by assessing individual microcapillary perfusion and tissue diffusivity.
The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and ...tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess the role of historical risk factors and novel magnetic resonance imaging (MRI) biomarkers in predicting outcomes in these patients. Patients diagnosed with LA-OPC were studied with diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline and at the 10th radiotherapy (RT) fraction. Clinical information was collected as well. The endpoint of the study was the development of disease progression, locally or distantly. Of the 97 patients enrolled, 68 were eligible for analysis. Disease progression was recorded in 21 patients (11 had loco-regional progression, 10 developed distant metastases). We found a correlation between N diameter and disease control (
= 0.02); features such as p16 status and extranodal extension only showed a trend towards statistical significance. Among perfusion MRI features, higher median values of K
both in primary tumor (T,
= 0.016) and lymph node (N,
= 0.003) and lower median values of v
(
= 0.018 in T,
= 0.004 in N) correlated with better disease control. K
P90 and N diameter were identified by MRMR algorithm as the best predictors of outcome. In conclusion, the association of non-invasive MRI biomarkers and patients and tumor characteristics may help in predicting disease behavior and patient outcomes in order to ensure a more customized treatment.
To investigate the predictive role of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings before salvage radiotherapy after radical prostatectomy (RP).
This retrospective study ...selected patients with biochemical failure (BF) after RP restaged with DCE-MRI. Patients underwent sRT in 30 fractions delivering 66-69 Gy and 73.5 Gy to the prostatic fossa and to the local failure as per DCE-MRI, respectively. Pelvic nodes were treated to 54 Gy in selected patients. The endpoint was BF after sRT.
In total, 236 patients were analyzed and 146 (61.9%) had presumed local failure at DCE-MRI: 54.8%, 23.8% and 21.4% were found at the vesico-urethral anastomosis (VUA), the bladder neck and the retro-vesical space, respectively. The presence of a local failure at DCE-MRI halved the risk of BF; VUA-only location and lesion volume were independently correlated with survival without evidence of biochemical failure (bNED) at multivariable analysis. For patients with VUA-only disease up to 0.4 cc, the 4-year-bNED was 94.6% (95%CI: 80.2-98.6%) as opposed to 80.9% (95%CI: 71.6-87.4%) and 73.7% (95%CI: 63.1-81.8%) for other lesions and no macrodisease, respectively.
DCE-MRI at restaging for BF after RP provides predictive and therapeutic information. Patients with small lesions at the VUA have an excellent prognosis after sRT.
Background
There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double‐blind study, we tested 4 natural ...agents, propolis, aloe vera, calendula, and chamomile versus placebo.
Methods
Patients undergoing concomitant chemo‐intensity‐modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w).
Results
One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%‐49% were assigned to the placebo group and 53%‐51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors.
Conclusion
The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed.
To investigate the correlation between histogram-based Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI) parameters and positron emission tomography with 18F-fluorodeoxyglucose ...(18F-FDG-PET) values in oropharyngeal squamous cell carcinoma (OPSCC), both in primary tumors (PTs) and in metastatic lymph nodes (LNs).
52 patients with a new pathologically-confirmed OPSCC were included in the present retrospective cohort study. Imaging including DCE-MRI and 18F-FDG PET/CT scans were acquired in all patients. Both PTs and the largest LN, if present, were volumetrically contoured. Quantitative parameters, including the transfer constants, Ktrans and Kep, and the volume of extravascular extracellular space, ve, were calculated from DCE-MRI. The percentiles (P), P10, P25, P50, P75, P90, and skewness, kurtosis and entropy were obtained from the histogram-based analysis of each perfusion parameter. Standardized uptake values (SUV), SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated applying a SUV threshold of 40%. The correlations between all variables were investigated with the Spearman-rank correlation test. To exclude false positive results under multiple testing, the Benjamini-Hockberg procedure was applied.
No significant correlations were found between any parameters in PTs, while significant associations emerged between Ktrans and 18F-FDG PET parameters in LNs.
Evident relationships emerged between DCE-MRI and 18F-FDG PET parameters in OPSCC LNs, while no association was found in PTs. The complex relationships between perfusion and metabolic biomarkers should be interpreted separately for primary tumors and lymph-nodes. A multiparametric approach to analyze PTs and LNs before treatment is advisable in head and neck squamous cell carcinoma (HNSCC).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess ...the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER
) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER
was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER
, respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5-85.4%). The model based on V65 (%) and XQ-Int
(integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71-88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER
with a fair to good accuracy.
Purpose: In our institution, stereotactic radiosurgery of multiple brain metastases is performed with the CyberKnife® (CK) device, using fixed/Iris collimators. In this study, nineteen fixed/Iris ...plans were recalculated with the multileaf collimator (MLC), to assess if it is possible to produce plans with comparable dosimetric overall quality. Materials and Methods: For consistent comparisons, MLC plans were re-optimized and re-normalized in order to achieve the same minimum dose for the total planning target volume (PTVtot). Conformation number (CN), homogeneity index (HI) and dose gradient index (DGI) metrics were evaluated. The dose to the brain was evaluated as the volume receiving 12 Gy (V12) and as the integral dose (ID). The normal tissue complication probability (NTCP) for brain radionecrosis was calculated as a function of V12. Results: The reoptimized plans were reviewed by the radiation oncologist and were found clinically acceptable according to the The American Association of Physicists in Medicine (AAPM) Task Group-101 protocol. However, fixed/Iris plans provided significantly higher CN (+8.6%), HI (+2.2%), and DGI (+44.0%) values, and significantly lower ID values (−35.9%). For PTVtot less than the median value of 2.58cc, fixed/Iris plans provided significantly lower NTCP values. On the other side, MLC plans provided significantly lower treatment times (−18.4%), number of monitor units (−33.3%), beams (−46.0%) and nodes (−21.3%). Conclusions: CK-MLC plans for the stereotactic treatment of brain multi metastases could provide an important advantage in terms of treatment duration. However, to contain the increased risk for brain radionecrosis, it could be useful to calculate MLC plans only for patients with large PTVtot.
To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately ...hypofractionated radiation therapy (MHRT) for localized prostate cancer.
Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143).
Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval CI 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer-related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates.
MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.
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