The use of Stereotactic Body Radiotherapy (SBRT) for bone metastases is increasing rapidly. Therefore, knowledge of the inter-observer differences in tumor volume delineation is essential to ...guarantee precise dose delivery. The aim of this study is to compare inter-observer agreement in bone metastases delineated on different imaging modalities.
Twenty consecutive patients with bone metastases treated with SBRT were selected. All patients received CT and MR imaging in treatment position prior to SBRT. Five observers from three institutions independently delineated gross tumor volume (GTV) on CT alone, CT with co-registered MRI and MRI alone. Four contours per imaging modality per patient were available, as one set of contours was shared by 2 observers. Inter-observer agreement, expressed in generalized conformity index CIgen, volumes of contours and contours center of mass (COM) were calculated per patient and imaging modality.
Mean GTV delineated on MR (45.9±52.0cm3) was significantly larger compared to CT–MR (40.2±49.4cm3) and CT (34.8±41.8cm3). A considerable variation in CIgen was found on CT (mean 0.46, range 0.15–0.75) and CT–MRI (mean 0.54, range 0.17–0.71). The highest agreement was found on MRI (mean 0.56, range 0.20–0.77). The largest variations of COM were found in anterior–posterior direction for all imaging modalities.
Large inter-observer variation in GTV delineation exists for CT, CT–MRI and MRI. MRI-based GTV delineation resulted in larger volumes and highest consistency between observers.
Purpose
Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid ...dysfunctions and diseases in Italy.
Methods
A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region
.
Results
Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013.
Conclusions
The results of this population-based study describe recent variations over time and between surrounding areas of indicators of ‘diagnostic pressure’ on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas.
Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we ...retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.
Bronchiolitis obliterans organizing pneumonia is an interstitial lung disease rarely occurring after radiotherapy probably due to an activation of autoimmune processes. Most cases have been described ...after postoperative radiotherapy for breast cancer. Corticosteroids represent the main treatment, prognosis is generally favorable. We described a case of bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for a recurrent lung cancer. Antibiotics and steroids were administered to solve the clinical picture. After three years, a new lesion at the right lung was found and treated with stereotactic ablative radiation therapy and concomitant long course of steroids with no recurrence of bronchiolitis obliterans organizing pneumonia. Bronchiolitis obliterans organizing pneumonia is a rare event after radiotherapy with undefined risk factors. In our case, steroids played an important role in management and, maybe, in preventing bronchiolitis obliterans organizing pneumonia recurrence after second course of stereotactic ablative radiation therapy.
La bronchiolite oblitérante avec organisation pneumonique est une pneumopathie interstitielle qui se manifeste après la radiothérapie, probablement à cause de l’activation d’un processus auto-immun. Plusieurs cas ont été décrits après une radiothérapie postopératoire pour cancer du sein. Les corticostéroïdes constituent le traitement de choix, le pronostic est généralement favorable. Nous rapportons un cas de bronchiolite oblitérante avec organisation pneumonique après radiothérapie en conditions stéréotaxiques pour cancer du poumon récidivant. Les antibiotiques et les corticostéroïdes ont été administrées pour résoudre le tableau clinique. Au bout de trois ans, une nouvelle métastase dans le poumon droit a été découverte, puis prise en charge par radiothérapie en conditions stéréotaxiques et une administration prolongée de corticostéroïdes sans réapparition de la bronchiolite oblitérante avec organisation pneumonique. La bronchiolite oblitérante avec organisation pneumonique est un événement rare sans facteurs de risque défini. Dans notre cas, les corticostéroïdes ont joué un rôle important pour le traitement et, probablement, pour prévenir un nouvel épisode de bronchiolite oblitérante avec organisation pneumonique après le deuxième cycle de radiothérapie en conditions stéréotaxiques.
To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and ...12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69–77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%;
P
= 0.002) and more high-volume target (75% vs 60%;
P
< 0.001) were included. Acute gastro-intestinal (GI) toxicity
G
> 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI
G
> 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity
G
> 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU
G
> 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU > 1 (
P
= 0.004) and for GI > 1 (
P
< 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.
Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the ...subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m
2
cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.
OZONE (O_3) is a controversial gas because, owing to its potent oxidant properties, it exerts damaging effects on the respiratory tract and yet it has been used for four decades as a therapy. While ...the disinfectant activity of O_3 is understandable, it is less clear how other biological effects can be elicited in human blood with practically no toxicity. On the other hand plasma and cells are endowed with a powerful antioxidant system so that a fairly wide range of O_3 concentrations between 40 and 80μ g/ml per gram of blood (˜0.83-1.66 mM) are effective but not deleterious. After blood ozonation total antioxidant status (TAS) and plasma protein thiol groups (PTG) decrease by 20% and 25%, respectively, while thiobarbituric acid reactive substances (TBARS) increases up to fivefold. The increase of haemolysis is negligible suggesting that the erythrocyte membrane is spared at the expense of other sacrificial substrates. While there is a clear relationship between the ozone dose and IL-8 levels, we have noticed that high TAS and PTG values inhibit the cytokine production. This is in line with the current idea that hydrogen peroxide, as a byproduct of O_3 decomposition, acts as a messenger for the cytokine induction.
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