Stereotactic Radiosurgery with Volumetric Modulated Arc Radiotherapy: Final Results of a Multi-arm Phase I Trial (DESTROY-2).

AIMS: To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. MATERIALS AND METHODS: The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/ß:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. CONCLUSION: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.

Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Stereotactic Body Reirradiation in Gynaecological Cancer: Outcomes and Toxicities from a Single Institution Experience.

AIMS: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. MATERIALS AND METHODS: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. RESULTS: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. CONCLUSIONS: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.

Volumetric Intensity-Modulated Arc Stereotactic Radiosurgery Boost in Oligometastatic Patients with Spine Metastases: a Dose-escalation Study.

AIMS: To report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases. MATERIALS AND METHODS: Oligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale. RESULTS: Fifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40-85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED α/ß10: 45.6 Gy), 14 patients received 10 Gy (total BED α/ß10: 51.2 Gy) and six patients received 12 Gy (total BED α/ß10: 57.6 Gy). The median follow-up time was over 70 months (range 2-240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography-computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively. CONCLUSION: A 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile.

Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis

IntroductionAim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases.MethodsWe separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated.ResultsData on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3–72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1–69 months) and 51.2%, respectively.ConclusionsData analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.

Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis.

INTRODUCTION: Aim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases. METHODS: We separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated. RESULTS: Data on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3-72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1-69 months) and 51.2%, respectively. CONCLUSIONS: Data analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.

Stereotactic body radiotherapy to lymph nodes in oligoprogressive castration-resistant prostate cancer patients: a post hoc analysis from two phase I clinical trials.

The prognosis of prostate cancer (PC) is generally favorable but the incidence of metastases is relatively high after the treatment of the primary tumor, especially in high-risk patients. Fractionated stereotactic body radiotherapy (SBRT) or single fraction stereotactic body radiosurgery (SRS) are emerging treatment options in this setting. However, data on SBRT/SRS in patients with metastatic castration-resistant PC (mCRPC) are largely lacking, particularly in subjects with nodal lesions. Therefore, we evaluated outcomes and toxicity recorded in mCRPC patients with nodal oligoprogression. Patients included in this analysis had ≤ 5 metastatic sites without visceral lesions and underwent SBRT/SRS on nodal metastases. Thirty-eight patients carrying out 61 nodal metastases were analyzed. The median SRS dose was 20 Gy (range 12-24 Gy) and the most common schedule was 20 Gy (44.8%). The median SBRT dose was 45 Gy (range 20-50 Gy) and the most common regimen was 45 Gy in 5 fractions (37.9%). Thirty-seven patients (97.4%) showed only grade 0-1 acute toxicity while one patient reported grade 2 dysphagia. In terms of late toxicity, one grade 2 laryngeal, one grade 1 skin and one grade 1 gastrointestinal toxicities were recorded. Two-year actuarial local control (LC), distant progression-free survival, progression-free survival (PFS) and overall survival were 94.0, 47.2, 47.2, and 90.2%, respectively. Two-year next line systemic therapy-free survival (NEST-FS) was 67.7%. In conclusion, the efficacy in terms of LC of SBRT/SRS in patients with nodal metastases from PC was confirmed. Moreover, this analysis suggests the efficacy in terms of PFS and NEST-FS also in the setting of oligoprogressive PC. In fact, about one-third of patients were free from progressive disease and two-third of subjects did not require hormonal therapy switch or discontinuation three years after treatment.

Improving dose delivery accuracy with EPID in vivo dosimetry: results from a multicenter study.

PURPOSE: To investigate critical aspects and effectiveness of in vivo dosimetry (IVD) tests obtained by an electronic portal imaging device (EPID) in a multicenter and multisystem context. MATERIALS AND METHODS: Eight centers with three commercial systems-SoftDiso (SD, Best Medical Italy, Chianciano, Italy), Dosimetry Check (DC, Math Resolution, LCC), and PerFRACTION (PF, Sun Nuclear Corporation, SNC, Melbourne, FL)-collected IVD results for a total of 2002 patients and 32,276 tests. Data are summarized for IVD software, radiotherapy technique, and anatomical site. Every center reported the number of patients and tests analyzed, and the percentage of tests outside of the tolerance level (OTL%). OTL% was categorized as being due to incorrect patient setup, incorrect use of immobilization devices, incorrect dose computation, anatomical variations, and unknown causes. RESULTS: The three systems use different approaches and customized alert indices, based on local protocols. For Volumetric Modulated Arc Therapy (VMAT) treatments OTL% mean values were up to 8.9% for SD, 18.0% for DC, and 16.0% for PF. Errors due to "anatomical variations" for head and neck were up to 9.0% for SD and DC and 8.0% for PF systems, while for abdomen and pelvis/prostate treatments were up to 9%, 17.0%, and 9.0% for SD, DC, and PF, respectively. The comparison among techniques gave 3% for Stereotactic Body Radiation Therapy, 7.0% (range 4.7-8.9%) for VMAT, 10.4% (range 7.0-12.2%) for Intensity Modulated Radiation Therapy, and 13.2% (range 8.8-21.0%) for 3D Conformal Radiation Therapy. CONCLUSION: The results obtained with different IVD software and among centers were consistent and showed an acceptable homogeneity. EPID IVD was effective in intercepting important errors.

Multiparametric MR imaging of the prostate at 1.5-T without endorectal coil using an 8 channel pelvic phased array: Is it still a viable option?

INTRODUCTION: The purpose of our work was to evaluate the feasibility of prostate multiparametric MR imaging at 1.5-T without endorectal coil using an 8 channel pelvic phased array coil. MATERIAL AND METHODS: A total of 154 patients who underwent mp-MRI were retrospectively included. Patients received a standardized mp-MRI, compliant with 2012 European Society of Uro-Radiology guidelines, with 1·5 T magnetic field strength and an 8 channel pelvic phased-array coil. Two blinded readers graded the image quality of mp-MRI on a three-point scale and they scored the prostate lesions according to PI-RADS v2. All PI-RADS of 4 or 5 underwent biopsy. A third radiologist and a pathologist verified the correspondence between the MRI images and the results of the biopsy. RESULTS: 64 (41.6%) patients showed a Pi-rads of 4 or 5. At biopsy, 79.7% showed a Gleason score ≥7, 12.5% showed a Gleason score of 6 and 7.8% showed a negative biopsy. In the group of Pi-rads ≤ 3, 12 patients underwent a biopsy with the following results: negative biopsy in 33.3%, atypical Small Acinar Proliferation in 16.7%, prostatic intraepithelial neoplasia in 25% and indolent PCa 25%. Mp-MRI in the identification of clinically significant cancer provided a low percentage of false positive (7.8%) while in 79.7% of cases it was capable to detect clinically significant prostate cancer. In 92.2% of patients mp-MRI identified a prostate cancer with a Gleason score ≥6. The inter-reader agreement was excellent in defining both the quality of the examination and the PI-RADS category (k = 0.83 and k = 0.70, respectively). CONCLUSIONS: mp-MRI at 1.5-T without endorectal coil using an 8 channel phased array is an appropriate tool for early detection of clinically significant prostate cancer. IMPLICATIONS FOR PRACTICE: 8 channel pelvic phased array is still an appropriate tool for early detection of clinically significant prostate cancer and for obtaining a reduction in overdiagnosis of indolent PCa.

Optical coherence tomography angiography in Purtscher-like retinopathy associated with dermatomyositis: a case report.

PURPOSE: To describe a multimodal imaging diagnosis of retinopathy in dermatomyositis. CASE PRESENTATION: A 21-year-old white woman with a history of fatigue and a cutaneous rash complained of visual impairment in her left eye. A funduscopic examination showed multiple confluent cotton-wool spots in both eyes. Swept source-optical coherence tomography presented macular edema in both eyes; optical coherence tomography angiography revealed superficial and deep capillary occlusion in all areas affected by cotton-wool spots; and fluorescein angiography showed vascular walls enhancement, veins dilatation, and capillary leakage. After large doses of intravenously administered glucocorticoid therapy, followed by a cyclophosphamide regimen, best corrected visual acuity returned to 20/20 in both eyes. CONCLUSIONS: This case report presents optical coherence tomography angiography clinical findings in a rare case of dermatomyositis-associated retinopathy, remarking the importance of a multi-imaging approach for a correct diagnosis and treatment of eye injuries, in order to avoid serious complications and permanent sequelae.

ECG-gated CT angiography of the thoracic aorta: the importance of evaluating the coronary arteries.

AIM: To evaluate the feasibility of coronary artery disease (CAD) evaluation using electrocardiogram-gated computed tomography CT of the thoracic aorta. MATERIALS AND METHODS: A total of 477 patients, who underwent CT angiography of the thoracic aorta, were included retrospectively. Dose-length products (DLP) were recorded. Two blinded readers graded image quality of the coronary arteries on a three-point scale. Coronary artery stenosis has only been reported if considered significant, i.e., ≥50%. The type of plaque responsible for the stenosis was considered. The normal distribution of the data was assessed using Shapiro-Wilk and Anderson-Darling tests. Results were expressed as means and standard deviations and percentages. Inter-reader agreements were analysed by calculating the intraclass correlation coefficient, and by using Cohen kappa statistics. RESULTS: The mean DLP was 566±90.4 mGy∙cm, corresponding to an effective dose of 9.6±1.5 mSv. Five point three percent of asymptomatic patients were positive for CAD with stenosis ≥50%. All patients with coronary stenosis presented with a soft plaque. Two anomalous coronary origins were found. The inter-reader agreement was excellent in defining both the quality of the examination and the degree of coronary stenosis (k=0.85). CONCLUSION: The opportunity to prove the presence of CAD in asymptomatic patients during a ECG-gated CT of the thoracic aorta can have an extremely important clinical impact, promoting the best therapeutic pathway for the patient. Therefore, coronary arteries should always be analysed carefully and reported in ECG-gated CT angiography of the thoracic aorta.

A validation study of a dedicated software for an automated in vivo dosimetry control in radiotherapy.

In vivo dosimetry (IVD) is the last step of a radiotherapy quality control program aimed to ensure that the dose delivered is in agreement with that prescribed. IVD procedures based on single detectors are time-consuming and impossible to use for the modern radiotherapy techniques, based on static or kinetic beams (modulated in intensity fluence); this means that more efficient and practical methods are highly recommended. The practical method SOFTDISO, based on the use of electronic portal image device (EPID), provides two tests (i) the R ratio between the reconstructed and the planned isocenter doses to verify an agreement within 5% and (ii) the γ-analysis of the EPID images, to verify γ% ≥ 90% and γmean ≤ 0.4. This paper reports the results of 11,357 IVD tests carried out for 823 patients treated by three-dimensional conformal radiation therapy and volumetric modulated arc therapy techniques. In particular, the dose disagreements are reported distinguishing two kinds of causes, those of (i) class 1 that includes the errors due to inadequate quality controls and (ii) the class 2, due to patient morphological changes. About the tests out of tolerance, 6% were by VMAT and 21% by 3DCRT, but taking into account the only class 1 of errors, i.e., removing the causes of class 2, only 7% of patients examined presented at least one of the three mean indexes out of tolerance. The workload for IVD on 9 patients/day per linac is about 52 min/day but recently, a new automated SOFTDISO version has been implemented to reduce the time to about 34 min/day.

Visual function improvement using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by retinal diseases.

BACKGROUND: To evaluate functional visual parameters using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by central or peripheral scotoma due to retinal diseases. Sixty patients were enrolled in this study: 30 patients affected by central scotoma, group 1, and 30 affected by peripheral scotoma, group 2. Black on White Best Corrected Visual Acuity (BW-BCVA), White on Black Best Corrected Visual Acuity (WB-BCVA), Mars Contrast Sensitivity (CS) and a Glare Test (GT) were performed to all patients. Test results with blue-violet filter, a short-pass yellow filter and with no filters were compared. RESULTS: All scores from test results increased significantly with blue-violet filters for all patients. The mean BW-BCVA increased from 0.30 ± 0.20 to 0.36 ± 0.21 decimals in group 1 and from 0.44 ± 0.22 to 0.51 ± 0.23 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The mean WB-BCVA increased from 0.31 ± 0.19 to 0.38 ± 0.23 decimals in group 1 and from 0.46 ± 0.20 to 0.56 ± 0.22 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The letter count for the CS test increased from 26.7 ± 7.9 to 30.06 ± 7.8 in group 1 (Mean ± SD, p = 0.0005) and from 31.5 ± 7.6 to 33.72 ± 7.3 in group 2 (Mean ± SD, p = 0.031). GT was significantly reduced: the letter count increased from 20.93 ± 5.42 to 22.82 ± 4.93 in group 1 (Mean ± SD, p < 0.0001) and from 24.15 ± 5.5 to 25.97 ± 4.7 in group 2 (Mean ± SD, p < 0.0001). Higher scores were recorded with the Blue filter compared to Yellow filter in all tests (p < 0.05). No significant differences in any test results could be detected between the Yellow filter and the No filter condition. CONCLUSIONS: The use of a combination of photocromic lens with a selective blue-violet light filter showed functional benefit in all evaluated patients.

Structure-function relationship in early diabetic retinopathy: a spatial correlation analysis with OCT and microperimetry.

PurposeTo study the correlation of the local ganglion cell layer-inner plexiform layer (GCL-IPL) thickness with corresponding retinal sensitivity as studied with microperimetry in patients with Type 2 diabetes and no signs of diabetic retinopathy.Patients and methodsWe analyzed 35 healthy subjects (68 eyes) and 26 Type 2 diabetic patients (48 eyes) with no signs of diabetic retinopathy. We tested best corrected visual acuity (BCVA), monocular and binocular constrast sensitivity (CS, Pelli - Robson chart) and retinal sensitivity with microperimetry, and acquired dense macular SD-OCT scans. We then studied the correlation between local GCL-IPL thickness and local sensitivity.ResultsMean BCVA was 1.09 (±1.03) decimals in diabetic subjects and 1.02 (±0.15) decimals in healthy subjects. Only binocular CS was significantly higher in healthy subjects (1.18±0.42 for healthy subjects, 1.62±0.63 for diabetic subjects). In both local and global analysis we observed higher GCL-IPL thickness and higher sensitivity in normal compared with diabetic subjects, but no difference reached significance (p<0.05). Using a mixed multivariate linear model, we found a significant correlation between retinal sensitivity and the correspondent GCL-IPL thickness in diabetic subjects (0.022±0.006 dB/µm, p=0.0007) but not in healthy subjects (-0.002±0.006 dB/µm, p=0.77).Conclusiondespite close similarities between the two groups, we found a significant difference in the structure-function relationship in diabetic subjects without diabetic retinopathy, suggesting that diabetes might act as an additional effect in the normal deterioration of the visual function related to the inner retina.

Step-and-Shoot IMRT by Siemens Beams: An EPID Dosimetry Verification During Treatment.

PURPOSE: This work reports the extension of a semiempirical method based on the correlation ratios to convert electronic portal imaging devices transit signals into in vivo doses for the step-and-shoot intensity-modulated radiotherapy Siemens beams. The dose reconstructed at the isocenter point Diso, compared to the planned dose, Diso,TPS, and a γ-analysis between 2-dimensional electronic portal imaging device images obtained day to day, seems to supply a practical method to verify the beam delivery reproducibility. METHOD: The electronic portal imaging device images were obtained by the superposition of many segment fields, and the algorithm for the Diso reconstruction for intensity-modulated radiotherapy step and shoot was formulated using a set of simulated intensity-modulated radiotherapy beams. Moreover, the in vivo dose-dedicated software was integrated with the record and verify system of the centers. RESULTS: Three radiotherapy centers applied the in vivo dose procedure at 30 clinical intensity-modulated radiotherapy treatments, each one obtained with 5 or 7 beams, and planned for patients undergoing radiotherapy for prostatic tumors. Each treatment beam was checked 5 times, obtaining 900 tests of the ratios R = Diso/Diso,TPS. The average R value was equal to 1.002 ± 0.056 (2 standard deviation), while the mean R value for each patient was well within 5%, once the causes of errors were removed. The γ-analysis of the electronic portal imaging device images, with 3% 3 mm acceptance criteria, showed 90% of the tests with Pγ < 1 ≥ 95% and γmean ≤ 0.5. The off-tolerance tests were found due to incorrect setup or presence of morphological changes. This preliminary experience shows the great utility of obtaining the in vivo dose results in quasi real time and close to the linac, where the radiotherapy staff may immediately spot possible causes of errors. The in vivo dose procedure presented here is one of the objectives of a project, for the development of practical in vivo dose procedures, financially supported by the Istituto Nazionale di Fisica Nucleare.

Choroidal Thickness Analysis in Patients with Usher Syndrome Type 2 Using EDI OCT.

To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), axial length (AL), automated visual field (VF), and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT) was 248.21 ± 79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient -0.7248179, p < 0.01). No statistically significant correlation was found between SFCT and BCVA, IOP, AL, VF, and RT. SFCT was reduced if compared to healthy subjects (p < 0.01). No difference was found when compared to choroidal thickness from nonsyndromic RP patients (p = 0.2138). Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.

Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2).

AIMS: To present the interim results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumours in different extracranial sites. MATERIALS AND METHODS: Patients were enrolled in different arms according to tumour site and clinical stage, and sequentially assigned to a given dose level. Acute toxicity, tumour response and early local control were investigated and reported. RESULTS: One hundred lesions in 65 consecutive patients (male/female: 30/35, median age: 66 years; range: 40-89) were treated. Of these 100 lesions, 21 were primary or metastatic lung tumours, 24 were liver metastases, 30 were bone metastases, 24 were nodal metastases and one was a primary vulvar melanoma. The prescribed dose ranged from 12 (BED(2Gy,α/ß:10) = 26.4 Gy) to 28 Gy (BED(2Gy,α/ß:10) = 106.4 Gy) to the planning target volume. Twenty-one patients (32.3%) experienced grade 1-2 acute toxicity, which was grade 2 in only two cases. The overall response rate based on computed tomography/magnetic resonance imaging was 52% (95% confidence interval 40.1-63.2%) and based on positron emission tomography scan was 90% (95% confidence interval 76.2-96.4%). As of November 2013, the median duration of follow-up was 11 months (range = 1-38). Recurrence/progression within the SRS-VMAT treated field was observed in nine patients (total lesions = 18): the inside SRS-VMAT field local control expressed on a per lesion basis was 87.8% at 12 months and 71.9% at 24 months. CONCLUSIONS: The maximum tolerable dose has not yet been reached in any study arm. SRS-VMAT resulted in positive early clinical results in terms of tumour response, local control rate and acute toxicity.

Quasi real time in vivo dosimetry for VMAT.

PURPOSE: Results about the feasibility of a method for quasi real time in vivo dosimetry (IVD) at the isocenter point for volumetric modulated arc therapy (VMAT) are here reported. The method is based on correlations between the EPID signal and the dose on the beam central axis. Moreover, the γ-analysis of EPID images was adopted to verify off-axis reproducibility of fractionated plan delivery. METHODS: An algorithm to reconstruct in vivo the isocenter dose, D(iso), for RapidArc treatments has been developed. 20 VMAT plans, optimized with two opposite arcs, for prostate, pancreas, and head treatments have been delivered by a Varian linac both to a conic PMMA phantom with elliptical section and to patients. The ratios R between reconstructed D(iso) and the planned doses were determined for phantom and patient irradiations adopting an acceptance criterion of ±5%. In total, 40 phantom checks and 400 patient checks were analyzed. Moreover, 3% and 3 mm criteria were adopted for portal image γ-analysis to assess patient irradiation reproducibility. RESULTS: The average ratio R, between reconstructed and planned doses for the PMMA phantom irradiations was equal to 1.007 ± 0.024. When the IVD method was applied to the 20 patients, the average R ratio was equal to 1.003 ± 0.017 and 96% of the tests were within the acceptance criteria. The portal image γ-analysis supplied 88% of the tests within the pass rates γ(mean) ≤ 0.4 and P(γ<1) ≥ 98%. All the warnings were understood comparing the CT and the cone beam CT images and in one case a patient's setup error was detected and corrected for the successive fractions. CONCLUSIONS: This preliminary experience suggests that the method is able to detect dosimetric errors in quasi real time at the end of the therapy session. The authors intend to extend this procedure to other pathologies with the integration of in-room imaging verification by cone beam CT.

Clinical implications of different calculation algorithms in breast radiotherapy: a comparison between pencil beam and collapsed cone convolution.

BACKGROUND: This investigation focused on the clinical implications of the use of the Collapsed Cone Convolution algorithm (CCC) in breast radiotherapy and investigated the dosimetric differences as respect to Pencil Beam Convolution algorithm (PBC). MATERIAL AND METHODS: 15 breast treatment plans produced using the PBC algorithm were re-calculated using the CCC algorithm with the same MUs. In a second step, plans were re-optimized using CCC algorithm with modification of wedges and beam weightings to achieve optimal coverage (CCCr plans). For each patient, dosimetric comparison was performed using the standard tangential technique (SWT) and a forward-planned IMRT technique (f-IMRT). RESULTS: The CCC algorithm showed significant increased dose inhomogeneity. Mean and minimum PTV doses decreased by 1.4% and 2.8% (both techniques). Mean V95% decreased to 83.7% and 90.3%, respectively for the SWT and f-IMRT. V95% was correlated to the ratio of PTV and lung volumes into the treatment field. The re-optimized CCCr plans achieved similar target coverage, but high-dose volume was significantly larger (V107%: 7.6% vs 2.3% (SWT), 7.1% vs 2.1% (f-IMRT). There was a significantly increase in the ipsilateral lung volume receiving low doses (V5 Gy: 31.3% vs 26.2% in SWT, 27.0% vs 23.0% in f-IMRT). MUs needed for PTV coverage in CCCr plans were higher by 3%. CONCLUSIONS: The PBC algorithm overestimated PTV coverage in terms of all important dosimetric metrics. If previous clinical experience are based on the use of PBC model, especially needed is discussion between medical physicists and radiation oncologists to fully understand the dosimetric changes.

An in-vivo dosimetry procedure for Elekta step and shoot IMRT.

PURPOSE: The aim of this work was to extend an in-vivo dosimetry (IVD) method, previously developed by the authors for 3D-conformal radiotherapy, to step and shoot IMRT treatments for pelvic tumors delivered by Elekta linacs. MATERIALS AND METHODS: The algorithm is based on correlation functions to convert EPID transit signals into in-vivo dose values at the isocenter point, Diso. The EPID images were obtained by the so-called "IMRT Dosimetric Weighting" mode as a superposition of many segment fields. This way each integral dosimetric image could be acquired in about 10 s after the end of beam delivery and could be processed while delivering the successive IMRT beams. A specific algorithm for Diso reconstruction especially featured for step and shoot IMRT was implemented using a fluence inhomogeneity index, FI, introduced to describe the degree of beam modulation with respect to open beams. A γ-analysis of 2D-EPID images obtained day to day, resulted rapid enough to verify the plan delivery reproducibility. RESULTS: Fifty clinical IMRT beams, planned for patients undergoing radiotherapy of pelvic tumors, were used to irradiate a homogeneous phantom. For each beam the agreement between the reconstructed dose, Diso, and the TPS computed dose, Diso,TPS, was well within 5%, while the mean ratio R = Diso/Diso,TPS resulted for 250 tests equal to 1.006 ± 0.036. The same beams were checked in vivo, i.e. during patient treatment delivery, obtaining 500 tests whose average R ratio resulted equal to 1.011 ± 0.042. The γ-analysis of the EPID images with 5% 3 mm criteria supplied 85% of the tests with pass rates γ(mean) ≤ 0.5 and P(γ<1) ≥ 90%.