Assessment of Residual Radioactivity by a Comprehensive Wireless, Wearable Device in Thyroid Cancer Patients Undergoing Radionuclide Therapy and Comparison With the Results of a Home Device: A Feasibility Study.

Objective: To investigate the feasibility of using a wireless wearable device (WD) in differentiated thyroid cancer (DTC) patients undergoing radionuclide therapy with I-131 (RAI) and protected hospitalization, this study compared the measurements of residual radioactivity obtained with those registered by a permanent environmental home device (HD). Methods: Twenty consecutive patients undergoing RAI hospitalized in restricted, controlled areas were enrolled. The patients underwent comprehensive monitoring of vital/nonvital parameters. We obtained 45580± 13 measurements from the WD, detecting the residual radioactivity for each patient during approximately 56 hours of hospitalization, collecting data 53 times per hour. The samples, collected during daily activities, were averaged every two hours, and the results correlated with those from the HD. Bland-Altman analysis was also used to evaluate the agreement between the two techniques. Results: A significant relationship between the WD and HD was observed (r = 0.96, p < 0.0001). Bland-Altman analysis recognized the agreement between measurements by the WD and HD. The mean value at the end of the first day of hospitalization was 80.81 microSv/h and 60.77 microSv/h (p = ns for WD and HD), whereas those at the end of the second day were 47.08 and 24.96 (p = ns). In the generalized linear model (GLM), a similar trend in performance across time was found with the two techniques. Conclusion: This study demonstrates good agreement between the residual radioactivity measures estimated by the WD and HD modalities, rendering them interchangeable. This approach will allow both the optimization of medical staff exposure and safer patient discharge. Abbreviations: wireless device (WD); differentiated thyroid cancer (DTC); radionuclide therapy with I-131 (RAI); home device (HD); generalized linear model (GLM).

Clinical radiobiology of head and neck cancer: the hypothesis of stem cell activation

Purpose To estimate and reduce uncertainties of a selfconsistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT). Methods Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (a) and the repair (b) radio-sensitivities were estimated together with the doubling time (Td) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (Tk) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results. Results The best estimate and the 95 % confidence intervals (95 % CIs) were: a = 0.24 Gy-1 (0.23–0.26), b = 0.023 Gy-2 (0.021–0.025), a/b = 10.6 Gy (8.4–12.6), Td = 3.5 days (3.1–3.9), Tk = 19.2 days (15.1–23.3), N = 7 9 107 (4 9 107 –1 9 108 ). From these data, the dose required to offset repopulation occurring in 1 day (Dprolif) and starting after Tk was also estimated as 0.69 Gy/day (0.52–0.86). Conclusions The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC (AU)

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Clinical radiobiology of head and neck cancer: the hypothesis of stem cell activation.

PURPOSE: To estimate and reduce uncertainties of a self-consistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT). METHODS: Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (α) and the repair (ß) radio-sensitivities were estimated together with the doubling time (T d) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (T k) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results. RESULTS: The best estimate and the 95 % confidence intervals (95 % CIs) were: α = 0.24 Gy(-1) (0.23-0.26), ß = 0.023 Gy(-2) (0.021-0.025), α/ß = 10.6 Gy (8.4-12.6), T d = 3.5 days (3.1-3.9), T k = 19.2 days (15.1-23.3), N = 7 × 10(7) (4 × 10(7)-1 × 10(8)). From these data, the dose required to offset repopulation occurring in 1 day (D prolif) and starting after T k was also estimated as 0.69 Gy/day (0.52-0.86). CONCLUSIONS: The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC.

The impact of computed tomography slice thickness on the assessment of stereotactic, 3D conformal and intensity-modulated radiotherapy of brain tumors

PURPOSE: To evaluate radiotherapy treatment planning accuracy by varying computed tomography (CT) slice thickness and tumor size. METHODS: CT datasets from patients with primary brain disease and metastatic brain disease were selected. Tumor volumes ranging from about 2.5 to 100 cc and CT scan at different slice thicknesses (1, 2, 4, 6 and 10 mm) were used to perform treatment planning (1-, 2-, 4-, 6- and 10-CT, respectively). For any slice thickness, a conformity index (CI) referring to 100, 98, 95 and 90 % isodoses and tumor size was computed. All the CI and volumes obtained were compared to evaluate the impact of CT slice thickness on treatment plans. RESULTS: The smallest volumes reduce significantly if defined on 1-CT with respect to 4- and 6-CT, while the CT slice thickness does not affect target definition for the largest volumes. The mean CI for all the considered isodoses and CT slice thickness shows no statistical differences when 1-CT is compared to 2-CT. Comparing the mean CI of 1- with 4-CT and 1- with 6-CT, statistical differences appear only for the smallest volumes with respect to 100, 98 and 95 % isodoses-the CI for 90 % isodose being not statistically significant for all the considered PTVs. CONCLUSIONS: The accuracy of radiotherapy tumor volume definition depends on CT slice thickness. To achieve a better tumor definition and dose coverage, 1- and 2-CT would be suitable for small targets, while 4- and 6-CT are suitable for the other volumes (AU)

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Clinically relevant quality assurance for intensity modulated radiotherapy plans: gamma maps and DVH-based evaluation.

PURPOSE: To explore a novel patient-dose DVH-based method for pretreatment dose quality assurance tests. METHODS: 20 IMRT plans for head-and-neck cancer patients were used. A comparison was performed between the planned dose distributions, the computed, and the reconstructed ones using the gamma-index (GI) method. The GI analysis was performed using both the 3%/3 mm and the 2%/2 mm criteria. RESULTS: No significant DVH-deviation was observed. Considering the 3%/3 mm criteria the mean GI% < 1 for the body and structures was significantly higher compared to 2%/2 mm criteria. CONCLUSIONS: Our results underline the importance of QA-methods based on DVH-metrics to predict the impact of delivered dose.

Clinically relevant quality assurance (QA) for prostate RapidArc plans: gamma maps and DVH-based evaluation.

The aim of this paper is to evaluate clinically relevant quality assurance (QA) tests for RapidArc prostate patients. 26 plans were verified by the COMPASS system that provides an independent angle response and a reconstruction of dose distribution in patient CT model. Plan data were imported from treatment planning system via DICOM. The fluencies, measured by a 2D detector, were used by COMPASS to forward calculate dose in CT patients and reconstruct dose-volume-histogram (DVH). The gamma analysis was performed, using both the criteria 3%-3-mm and 2%-2 mm, for the whole grid patient and the per-structure volume. A DVH-based analysis was accomplished for target and organs-at-risk (OAR). The correlation between gamma passing rates and DVH discrepancies was performed using Pearson's test. Sensitivity, specificity and accuracy of whole and per-structure gamma method were calculated. No significant DVH deviation was observed for target and OAR. Weak correlation between gamma passing rates and dosimetric deviations was observed, all significant r-values were negative. The whole gamma method shows lack of sensitivity to detect dosimetric deviations >5%. Instead, a better balance between sensitivity and specificity was obtained employing per structure gamma both with 3%-3 mm and 2%-2 mm criteria. Because of the poor correlation between DVH goals and gamma passing rates, we encourage the DVH-based gamma passing rates, when it is possible. At least, a gamma method specific for structure was strongly suggested.

Volumetric and dosimetric assessment by cone-beam computed tomography scans in head and neck radiation therapy: a monitoring in four phases of treatment.

Due to the anatomical changes frequently occurring during the course of head and neck (H&N) cancer radiotherapy, the dose distribution, which was actually delivered to the patient, might significantly differ from that planned. The aim of this paper is to investigate these volumetric changes and the resulting dosimetric implications on organs at risk (OARs) and clinical target volumes (CTVs) by cone beam computed tomography (CBCT) scans throughout the treatment. Ten H&N patients, treated by Intensity Modulated Radiotherapy, were analyzed. CTVs and OARs were delineated on four CBCT, acquired at the 10(th), 15(th), 20(th) and 25(th) treatment session, and then compared with the ones at planning CT. The planned beams were applied to each CBCT to recalculate the dose distribution and the corresponding dose volume histograms were compared with those generated on planning CT. To evaluate the HU discrepancies between the conventional CT and CBCT images we used a Catphan(r) 504, observing a maximum discrepancy of about 30 HU. We evaluated the impact of this HU difference in dose calculation and a not clinically relevant error, within 2.8%, was estimated. No inhomogeneity correction was used. The results showed an increased CTV mean dose (Dmean) of about 3% was found, without significant reduction in volume. Due to the parotids' shrinkage (up to 42%), significant dosimetric increases were observed: ipsilateral gland at 15th CBCT (Dmean by 18%; V30 by 31%); controlateral gland at the 10(th) CBCT (Dmean by 12.2%; V30 by 18.7%). For the larynx, a significant increase of volume was found at the 20th (15.7%) and 25th CBCT (13.3%) but it complied with dose constraint. The differences observed for the spinal cord and mandible maximum doses were not clinically relevant. In conclusion, the dosimetric analysis on CBCT can help clinicians to monitor treatment progress and to evaluate whether and when a new plan is necessary. The main benefit of replanning could be to preserve the parotids and our data support the hypothesis that the 3rd week of radiotherapy should be a check point for parotids.

The impact of computed tomography slice thickness on the assessment of stereotactic, 3D conformal and intensity-modulated radiotherapy of brain tumors.

PURPOSE: To evaluate radiotherapy treatment planning accuracy by varying computed tomography (CT) slice thickness and tumor size. METHODS: CT datasets from patients with primary brain disease and metastatic brain disease were selected. Tumor volumes ranging from about 2.5 to 100 cc and CT scan at different slice thicknesses (1, 2, 4, 6 and 10 mm) were used to perform treatment planning (1-, 2-, 4-, 6- and 10-CT, respectively). For any slice thickness, a conformity index (CI) referring to 100, 98, 95 and 90 % isodoses and tumor size was computed. All the CI and volumes obtained were compared to evaluate the impact of CT slice thickness on treatment plans. RESULTS: The smallest volumes reduce significantly if defined on 1-CT with respect to 4- and 6-CT, while the CT slice thickness does not affect target definition for the largest volumes. The mean CI for all the considered isodoses and CT slice thickness shows no statistical differences when 1-CT is compared to 2-CT. Comparing the mean CI of 1- with 4-CT and 1- with 6-CT, statistical differences appear only for the smallest volumes with respect to 100, 98 and 95 % isodoses-the CI for 90 % isodose being not statistically significant for all the considered PTVs. CONCLUSIONS: The accuracy of radiotherapy tumor volume definition depends on CT slice thickness. To achieve a better tumor definition and dose coverage, 1- and 2-CT would be suitable for small targets, while 4- and 6-CT are suitable for the other volumes.

Estimate of the accelerated proliferation by protein tyrosine phosphatase (PTEN) over expression in postoperative radiotherapy of head and neck squamous cell carcinoma

PURPOSE: To estimate the impact of PTEN expression in terms of effective doubling time (T(d)) and dose per fraction which compensates the accelerated proliferation during the radiotherapy (D(prolif)) when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data were carried out from a recent paper comparing the local control rate (LCR) for patients with HNSCC that underwent a conventional (p-CF) or accelerated radiotherapy (p-CAIR) and a pretreatment assessment of PTEN expression. The impact of PTEN over expression was assessed using the Clinical Efficacy Factor (C) and assuming a plausible range of intrinsic radiosensitivity (α). Statistical analysis was made by evaluating the LCR from Kaplan-Meier curves and log-rank test with significance of 0.05. RESULTS: C indexes were 1.46 and 0.23 for the high- versus low-PTEN group, corresponding to a considerable reduction of doubling time of more than six times (6.6 versus 42.2 days). The median estimate of D(prolif) was 0.51 versus 0.08 Gy/day if referred to a median value in the adopted range of α. CONCLUSIONS: The PTEN expression has a significant implication on the clinical management of these patient groups. Our data support the hypothesis that the high-PTEN group would benefit from a hypo-fractionation with a reduction of the OTT to compensate for the increase in the proliferation rate, while the low-PTEN group could benefits from a hyper-fractionation which would result in a reduced toxicity for all the organs at risk (AU)

Clinical target volume definition for glioblastoma radiotherapy planning: magnetic resonance imaging and computed tomography

PURPOSE: To assess the differences between the target delineation using computed tomography (CT) and imaging fusion CT/magnetic resonance imaging (MRI) for the radiotherapy planning of glioblastoma. METHODS: One hundred-twenty gross tumor volume and clinical target volume on CT and MRI (GTVCT/CTVCT, GTVMRI/CTVMRI, respectively) were contoured and evaluated. The treatments planning (total dose 60 Gy) based on CTVCT were analysed in terms of percentage of CTVCT and CTVMRI receiving 95 % of the prescribed dose (V95-CTVCT, V95-CTVMRI). RESULTS: GTVs and CTVs contoured on MRI were significantly larger than those delineated on CT (p = 0.0003, p = 0.0006, respectively). Nighty-two percent of CTVCT was coincident with the CTVMRI and 8 % was normal tissue; 20 % of CTVMRI, considered as tumor volume, was not included on CTVCT. The V95-CTVMRI was significantly lower than the V95-CTVCT (p = 0.0005). CONCLUSIONS: In the delineation of glioblastoma target volume, fusion CT/MRI was preferred. The CT only is insufficient for the CTV dose coverage (AU)

Planning target volume assessment in lung tumors dring 3D conformal radiotherapy by means of an aSi electronic portal imaging device in cine mode

PURPOSE: The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). METHODS: Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID was used in cine mode acquisition: acquired images were used to the aim. RESULTS AND CONCLUSIONS: Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool (AU)

Cone-beam computed tomography dose monitoring during intensity-modulated radiotherapy in head and neck cancer: parotid glands

PURPOSE: To evaluate the dosimetric changes of parotid glands (PG) during a course of intensity-modulated radiotherapy (IMRT) in head and neck (H&N) cancer patients. METHODS: Ten patients with H&N cancer treated by IMRT were analyzed. The original treatment plan (CT(plan)) was transferred to cone-beam computed tomography (CBCT) acquired at the 15th and 20th treatment day (CBCT(plan) I and II, respectively). The PG mean dose (D(mean)), the dose to 50 % of the volume, and the percent of volume receiving 30 and 50 Gy were measured by the dose volume histogram. RESULTS: 30 IMRT plans were evaluated (3 plans/patient). All dosimetric end points increased significantly for both PG only when CT(plan) was compared to CBCT(plan) I. The D(mean) increased significantly only for ipsilateral PG (p = 0.02) at week 3. CONCLUSION: During a course of IMRT, CBCT is a feasible method to heck the PG dosimetric variations. Perhaps, the 3rd week of radiotherapy could be considered as the time-check-point (AU)

Estimate of the accelerated proliferation by protein tyrosine phosphatase (PTEN) over expression in postoperative radiotherapy of head and neck squamous cell carcinoma.

PURPOSE: To estimate the impact of PTEN expression in terms of effective doubling time (T(d)) and dose per fraction which compensates the accelerated proliferation during the radiotherapy (D(prolif)) when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data were carried out from a recent paper comparing the local control rate (LCR) for patients with HNSCC that underwent a conventional (p-CF) or accelerated radiotherapy (p-CAIR) and a pretreatment assessment of PTEN expression. The impact of PTEN over expression was assessed using the Clinical Efficacy Factor (C) and assuming a plausible range of intrinsic radiosensitivity (α). Statistical analysis was made by evaluating the LCR from Kaplan-Meier curves and log-rank test with significance of 0.05. RESULTS: C indexes were 1.46 and 0.23 for the high- versus low-PTEN group, corresponding to a considerable reduction of doubling time of more than six times (6.6 versus 42.2 days). The median estimate of D(prolif) was 0.51 versus 0.08 Gy/day if referred to a median value in the adopted range of α. CONCLUSIONS: The PTEN expression has a significant implication on the clinical management of these patient groups. Our data support the hypothesis that the high-PTEN group would benefit from a hypo-fractionation with a reduction of the OTT to compensate for the increase in the proliferation rate, while the low-PTEN group could benefits from a hyper-fractionation which would result in a reduced toxicity for all the organs at risk.

Clinical target volume definition for glioblastoma radiotherapy planning: magnetic resonance imaging and computed tomography.

PURPOSE: To assess the differences between the target delineation using computed tomography (CT) and imaging fusion CT/magnetic resonance imaging (MRI) for the radiotherapy planning of glioblastoma. METHODS: One hundred-twenty gross tumor volume and clinical target volume on CT and MRI (GTVCT/CTVCT, GTVMRI/CTVMRI, respectively) were contoured and evaluated. The treatments planning (total dose 60 Gy) based on CTVCT were analysed in terms of percentage of CTVCT and CTVMRI receiving 95 % of the prescribed dose (V95-CTVCT, V95-CTVMRI). RESULTS: GTVs and CTVs contoured on MRI were significantly larger than those delineated on CT (p = 0.0003, p = 0.0006, respectively). Nighty-two percent of CTVCT was coincident with the CTVMRI and 8 % was normal tissue; 20 % of CTVMRI, considered as tumor volume, was not included on CTVCT. The V95-CTVMRI was significantly lower than the V95-CTVCT (p = 0.0005). CONCLUSIONS: In the delineation of glioblastoma target volume, fusion CT/MRI was preferred. The CT only is insufficient for the CTV dose coverage.

Planning target volume assessment in lung tumors during 3D conformal radiotherapy by means of an aSi electronic portal imaging device in cine mode.

PURPOSE: The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). METHODS: Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID was used in cine mode acquisition: acquired images were used to the aim. RESULTS AND CONCLUSIONS: Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

[Adjuvant radiochemotherapy in the elderly affected by glioblastoma: single-institution experience and literature review]. / Radiochemioterapia adiuvante nei pazienti anziani affetti da glioblastoma: esperienza di un singolo istituto e revisione della letteratura.

PURPOSE: Radiochemotherapy (RCT) is the standard adjuvant treatment for patients affected by glioblastoma (GBM). As there is no evidence in elderly patients with GBM, combined, single modality or best supportive care is used. The aim of this retrospective study was to evaluate acute toxicity and outcome of elderly patients with GBM treated with RCT with temozolomide (TMZ). MATERIALS AND METHODS: Patients >65 years with newly diagnosed GBM who underwent surgery or biopsy and RCT were evaluated. Recursive Partitioning Analysis (RPA) class and National Cancer Institute--Common Toxicity Criteria (NCI-CTC) version 3 were used to classify patients and evaluate acute toxicity, respectively. RESULTS: From April 2005 to January 2011, 35 patients (18 women and 17 men) with GBM were treated at our institution. Only 31.43% of cases underwent complete resection. Median progression-free survival (PFS) was 8 months and median overall survival (OS) 13 months. At univariate and multivariate analysis, only RPA class correlated with OS (p=0.01, p=0.03, respectively). During RCT, toxicity was mild (thrombocytopaenia G3-4, 11.43%; neurological toxicity, G3-4, 8.57%). CONCLUSIONS: Our data suggest that RCT with TMZ seems to produce a better outcome with a mild toxicity profile in elderly patients affected by GBM.

Cone-beam computed tomography dose monitoring during intensity-modulated radiotherapy in head and neck cancer: parotid glands.

PURPOSE: To evaluate the dosimetric changes of parotid glands (PG) during a course of intensity-modulated radiotherapy (IMRT) in head and neck (H&N) cancer patients. METHODS: Ten patients with H&N cancer treated by IMRT were analyzed. The original treatment plan (CT(plan)) was transferred to cone-beam computed tomography (CBCT) acquired at the 15th and 20th treatment day (CBCT(plan) I and II, respectively). The PG mean dose (D(mean)), the dose to 50 % of the volume, and the percent of volume receiving 30 and 50 Gy were measured by the dose volume histogram. RESULTS: 30 IMRT plans were evaluated (3 plans/patient). All dosimetric end points increased significantly for both PG only when CT(plan) was compared to CBCT(plan) I. The D(mean) increased significantly only for ipsilateral PG (p = 0.02) at week 3. CONCLUSION: During a course of IMRT, CBCT is a feasible method to check the PG dosimetric variations. Perhaps, the 3rd week of radiotherapy could be considered as the time-check-point.

Parotid gland volumetric changes during intensity-modulated radiotherapy in head and neck cancer.

OBJECTIVE: To evaluate volumetric changes of parotid glands (PGs) during intensity-modulated radiotherapy (IMRT) in head and neck cancer patients. METHODS: During IMRT all patients underwent kilovolt cone-beam CT (CBCT) scans to verify the set-up positioning in a protocol study. On each CBCT scan, the PGs were retrospectively contoured and evaluated with a dose-volume histogram. RESULTS: From February to June 2011, 10 patients were enrolled. 140 CBCT scans were registered (280 PGs): for each patient, a median of 14 CBCT scans were performed (range 14-16). At the start of radiation, the average volume for ipsilateral PGs (iPGs) was 18.77 ml (range 12.9-31.2 ml), whereas for contralateral PGs (cPGs) it was 16.63 ml (range 8.3-28.7 ml). At the last CBCT scan, the average volume loss was 43.5% and 44.0% for the iPG and cPG, respectively. When we analysed the percentage of volume loss, we observed that the volume decreased by linear regression (r(2)=0.92 for iPG; r(2)=0.91 for cPG), with an average volume loss rate of 1.5% per day for both PGs. During the third week of treatment the volume of both PGs reduced by 24-30%. CONCLUSION: Our data show that, during IMRT, the shrinkage of PGs should be taken into account. A replan could be indicated in the third week of radiotherapy.