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97. Towards a dose-response correlation in radioiodine therapy of hyperthyroidism from nodular thyroid disease
Abstracts / Physica Medica 56 (2018) 59–132
operative activities. For the same number of patients, even considering a 8 hours/day standing at 1.5 m from the patient bed, the worker received dose is around 0.65 mSv/y. Attenuation properties for selected materials were measured and agree with simulated results. Main contribution to exposure comes from X-c radiation, BS is almost negligible from radiation protection point of view. https://doi.org/10.1016/j.ejmp.2018.04.105
121
absorbed dose is lower than that at a depth of 3 = mm at the energies considered.
References 1. L’ICRP ‘‘Statement on Tissue Reactions”, Approved by the Commission on April 21, 2011. 2. ICRP 103, Ann. ICRP 37 (2-4), 2007. https://doi.org/10.1016/j.ejmp.2018.04.106
96. Evaluation of the equivalent dose to the crystalline lens by dose equivalent Hp(3) M. Marcantonini, F. Pascolini, A.R. Bernardini, A. Brughini, A. Cavalli, R. Tarducci Santa Maria della Misericordia Hospital, Medical Physics Department, Perugia, Italy Purpose . Individual dosimetry provides the tools for measuring doses from ionizing radiation of exposed workers. Recent scientific and epidemiological evidence highlights the need for adequate measures to protect the eye with particular regard to the crystalline lens [1]. The ICRP 103 proposes a depth of d = 3 mm for monitoring the crystalline dose (Hp(3)), stating that also the Hp(0.07) with calibration on slab can be used [2]. In our Dosimetry Service the operating quantity Hp (3) has been introduced and compared with Hp(0.07). Methods. A SLAB phantom calibration was performed at a LAT center in terms of Hp (3). The type of dosimeter is ext-rad TLD-100 of Lithium Fluoride LiF:Mg,Ti. Dosimeters were sent to be irradiated in Hp(3) with narrow photon beam at various energies. The irradiation parameters are in the Table. Hp(0.07) and Hp(3) were measured for 26 workers. The monthly measures collected relate to the semester January-June 2017. Results. The Figure shows for each operator the sum of the Hp (0.07) (red) and the Hp(3) (blue). The sum of the Hp(3) is greater than the sum of the Hp(0.07) as well as every single monthly value. Percentage differences were calculated between all the values of the Hp(0.07) and the Hp(3) and the average value is 10% ± 3%. Conclusions. In the same conditions of irradiation Hp(3) is greater than Hp(0.07). Expected result as to a depth of d = 0.07 mm the
97. Towards a dose-response correlation in radioiodine therapy of hyperthyroidism from nodular thyroid disease M. Pacilio a, G. Ventroni b, V. Frantellizzi c, B. Cassano d, T. Montesano c, C. Borrazzo c,e, C. Basile f, L. Mango b, G. De Vincentis c a
Azienda Ospedaliera Universitaria Policlinico Umberto I, Medical Physics Division, Rome, Italy b Azienda Ospedaliera San Camillo Forlanini, Department of Nuclear Medicine, Rome, Italy c ‘‘Sapienza” University of Rome, Department of Radiological, Oncological and Anatomo Pathological Sciences, Rome, Italy d ‘‘Sapienza” University of Rome, Postgraduate School of Medical Physics, Rome, Italy e ‘‘Sapienza” University of Rome, Department of Public Health and Infectious Disease, Rome, Italy f Agenzia per l’Italia Digitale, Area Trasformazione Digitale, Rome, Italy Purpose. Dosimetric treatment optimization is recommended for radioiodine therapy of hyperthyroidism. However, many clinicians still claim that fixed activity administrations yield analogous effectiveness, sparing time-consuming pretherapeutic studies. The possibility to establish a dose-response correlation was here investigated, highlighting the added value of patient-specific dosimetry. Methods. 374 patients affected by autonomous thyroid nodule, or multinodular goitre – presenting abnormal blood tests (TSH, and/or FT3, FT4) – were treated. Post-therapy follow-up lasted for at least 1 year. 187 patients were treated with an empiric methodology (not basing on a pre-treatment dosimetric study). 187 patients underwent dosimetry-based treatments (collecting just three biokinetics
122
Abstracts / Physica Medica 56 (2018) 59–132
points), including also 67 treatments based on a biologically effective dose (BED) prescription. The normality of blood tests at 1 year from the therapy, after the first treatment, was evaluated. The BED was also used in the result analysis for all dosimetry-based treatments. Statistical analysis was performed by Mann-Withney and Chisquared test, univariate receiver operating characteristics (ROC) analysis, and interpolation of dose–response data by a logistic model. Results. Dosimetric differences between the unhealed and the healed group (p = 0.0067) resulted from the 120 treatments based on absorbed dose prescriptions, also after conversion of the absorbed dose values in BED (p = 0.0049): the Area-under-curve (AUC) was 0.758 and 0.770, respectively. No significant differences were observed for the healing probability between the BED- or absorbed dose-based treatments (p = 0.423). Considering the total 187 dosimetry-based treatments, the absorbed dose/BED-response curves showed regular trends with r-value of 0.979 and 0.977, respectively. The absorbed dose associated to a healing probability of 50% and 95%, was 42.6 Gy and 242.3 Gy, respectively. The probability of recurrence was 9.6%, exactly half of that associated to the empiric treatment group (19.3%, p = 0.0081). Conclusions. Patient-specific dosimetry has proven to increase therapeutic effectiveness, reducing the recurrence frequency and the need of repeated treatments. https://doi.org/10.1016/j.ejmp.2018.04.107
98. Patient-specific estimation of the red marrow extracellular fluid fraction for improving the accuracy of red marrow dosimetry in radioimmunotherpy M. Pacilio a, C. Borrazzo b,c, N. Galea c, C. Basile d, I. Carbone c a Azienda Ospedaliera Universitaria Policlinico Umberto I, Medical Physics Division, Rome, Italy b Sapienza University of Rome, Department of Radiological, Oncological and Pathological Science, Rome, Italy c Sapienza University of Rome, Department of Public Health and Infectious Disease, Rome, Italy d Area Trasformazione Digitale, Agenzia per l’Italia Digitale, Rome, Italy
Purpose. The red marrow (RM) is the dose-limiting organ in radioimmunotherapy. The RM dosimetry is usually calculated by radioactivity concentrations of blood samples: RM kinetics is derived multiplying the blood kinetics by the ‘‘red marrow-to-blood activity concentration ratio” (RMBLR), calculated by patient-specific RM extracellular fluid fraction (RMECFF) and hematocrit (HCT) i.e., RMBLR ¼ RMECFF/(1-HCT) [1]. Preliminarily, the possible use of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI) for estimating the patient-specific RMECFF was here investigated. Methods. 9 patients (5 men, 4 women) studied with CEMRI for cardiac disorders were examined. Pre- and post-contrast T1 mapping by MOLLI (modified Look-Locker inversion-recovery) sequences was performed, and the extracellular volume fraction (ECV) map was calculated by a novel method - based on a Fast Non-linear Least Squares (FNLS) algorithm. The mean ECV of the spongiosa volume (SV) inside the dorsal vertebra at the heart level was obtained as mean value in a region-of-interest (ROI) lying wholly within the SV. Results. The mean ECV of the SV was (mean[range]): 29.9[24.0– 35.3]%. Considering the ECV as a preliminary estimation of the RMECFF, and accounting also for the patient HCT values (ranging from 0.340 up to 0.499), the mean RMBLR was 0.430[0.316–0.546], in a good agreement with the range of 0.2–0.4 generally reported
in the literature (even though values sometimes well outside this range were also observed) [1]. Conclusion. The CEMRI is accurate and very promising for patient-specific RMECFF estimations. Accuracy improvements by MOLLI sequence optimisation, or correction for the presence of trabecular bone and fatty tissue into the SV, are currently under investigation.
Reference 1. Sgouros G. Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. J Nucl Med 1993;34:689–94. https://doi.org/10.1016/j.ejmp.2018.04.108
99. Absorbed dose correlates with metabolic response to radioembolization of liver metastases with resin 90Ymicrospheres M.E. Ferrari a, F. Botta a, F. Guerriero b, C. Garibaldi a, M. Colandrea a, C.M. Grana a, G. Varano a, G. Bonomo a, F. Orsi a, M. Cremonesi a a b
Istituto Europeo di Oncologia, Milano, Italy Ulss 3 Serenissima, Venezia Mestre, Italy
Purpose. To investigate possible correlation between absorbed dose (AD) and tumour response by means of Tumour Control Probability (TCP) in liver metastases treated with radioembolization (RE) with resin 90Y-microspheres. To assess response, the analysis of parameters from FDG-PET/CT has been preferred to RECIST criteria as metabolic response has proven to anticipate morphologic response. Methods. Patients with chemo-refractory liver metastases from solid tumours scheduled to receive RE underwent FDG-PET/CT scan before and 6 weeks after RE. 99mTc-MAA (75–111 MBq) were injected 2 weeks before RE to perform dosimetry based on SPECT fused to contrast CT. Response assessment was based on PERCIST criteria. Variation (%) of PET parameters versus basal examination were evaluated to establish Complete-Response (CR), Partial-Response (PR), Stable-Disease (SD), Progressive-Disease (PD). Results. 22 patients with hepatic lesions from colon-rectal (11), breast (7), ovary (1), endometrial (1), parotid (1) cancer, cholangiocarcinoma (1) were suitable for analysis. All patients received a single RE treatment (median activity: 1.7 GBq; range: 0.6–2.9 GBq). Median (range) tumour AD: 100(30–443) Gy. Metabolic response rate of lesions based on PERCIST were: CR = 31%; PR = 28%; SD = 24%; PD = 17%. Two different TCP curves were obtained by probit regression when considering: i) endpoint-1: PR or CR; ii) endpoint2: CR only (p < 0.01 in both cases). For tumour AD> = 220 Gy only CR were observed. TCP of 50%, 75%, 100% were obtained at: i) 108, 120, 165 Gy; ii) 135, 160, 225 Gy. Conclusions. Despite the variety of primary tumours, relatively low cohort of patients, and uncertainty of dosimetry with 99mTcMAA, our preliminary data provided evidence of correlation between response based on PET/CT and AD. These encouraging results need to be confirmed with more ample dataset and, possibly, tumour type differentiation. Other PET/CT parameters such as the metabolic tumour volume and tumour lesion glycolysis are being considered for comparison with PERCIST and possible improved correlations. https://doi.org/10.1016/j.ejmp.2018.04.109
operative activities. For the same number of patients, even considering a 8 hours/day standing at 1.5 m from the patient bed, the worker received dose is around 0.65 mSv/y. Attenuation properties for selected materials were measured and agree with simulated results. Main contribution to exposure comes from X-c radiation, BS is almost negligible from radiation protection point of view. https://doi.org/10.1016/j.ejmp.2018.04.105
121
absorbed dose is lower than that at a depth of 3 = mm at the energies considered.
References 1. L’ICRP ‘‘Statement on Tissue Reactions”, Approved by the Commission on April 21, 2011. 2. ICRP 103, Ann. ICRP 37 (2-4), 2007. https://doi.org/10.1016/j.ejmp.2018.04.106
96. Evaluation of the equivalent dose to the crystalline lens by dose equivalent Hp(3) M. Marcantonini, F. Pascolini, A.R. Bernardini, A. Brughini, A. Cavalli, R. Tarducci Santa Maria della Misericordia Hospital, Medical Physics Department, Perugia, Italy Purpose . Individual dosimetry provides the tools for measuring doses from ionizing radiation of exposed workers. Recent scientific and epidemiological evidence highlights the need for adequate measures to protect the eye with particular regard to the crystalline lens [1]. The ICRP 103 proposes a depth of d = 3 mm for monitoring the crystalline dose (Hp(3)), stating that also the Hp(0.07) with calibration on slab can be used [2]. In our Dosimetry Service the operating quantity Hp (3) has been introduced and compared with Hp(0.07). Methods. A SLAB phantom calibration was performed at a LAT center in terms of Hp (3). The type of dosimeter is ext-rad TLD-100 of Lithium Fluoride LiF:Mg,Ti. Dosimeters were sent to be irradiated in Hp(3) with narrow photon beam at various energies. The irradiation parameters are in the Table. Hp(0.07) and Hp(3) were measured for 26 workers. The monthly measures collected relate to the semester January-June 2017. Results. The Figure shows for each operator the sum of the Hp (0.07) (red) and the Hp(3) (blue). The sum of the Hp(3) is greater than the sum of the Hp(0.07) as well as every single monthly value. Percentage differences were calculated between all the values of the Hp(0.07) and the Hp(3) and the average value is 10% ± 3%. Conclusions. In the same conditions of irradiation Hp(3) is greater than Hp(0.07). Expected result as to a depth of d = 0.07 mm the
97. Towards a dose-response correlation in radioiodine therapy of hyperthyroidism from nodular thyroid disease M. Pacilio a, G. Ventroni b, V. Frantellizzi c, B. Cassano d, T. Montesano c, C. Borrazzo c,e, C. Basile f, L. Mango b, G. De Vincentis c a
Azienda Ospedaliera Universitaria Policlinico Umberto I, Medical Physics Division, Rome, Italy b Azienda Ospedaliera San Camillo Forlanini, Department of Nuclear Medicine, Rome, Italy c ‘‘Sapienza” University of Rome, Department of Radiological, Oncological and Anatomo Pathological Sciences, Rome, Italy d ‘‘Sapienza” University of Rome, Postgraduate School of Medical Physics, Rome, Italy e ‘‘Sapienza” University of Rome, Department of Public Health and Infectious Disease, Rome, Italy f Agenzia per l’Italia Digitale, Area Trasformazione Digitale, Rome, Italy Purpose. Dosimetric treatment optimization is recommended for radioiodine therapy of hyperthyroidism. However, many clinicians still claim that fixed activity administrations yield analogous effectiveness, sparing time-consuming pretherapeutic studies. The possibility to establish a dose-response correlation was here investigated, highlighting the added value of patient-specific dosimetry. Methods. 374 patients affected by autonomous thyroid nodule, or multinodular goitre – presenting abnormal blood tests (TSH, and/or FT3, FT4) – were treated. Post-therapy follow-up lasted for at least 1 year. 187 patients were treated with an empiric methodology (not basing on a pre-treatment dosimetric study). 187 patients underwent dosimetry-based treatments (collecting just three biokinetics
122
Abstracts / Physica Medica 56 (2018) 59–132
points), including also 67 treatments based on a biologically effective dose (BED) prescription. The normality of blood tests at 1 year from the therapy, after the first treatment, was evaluated. The BED was also used in the result analysis for all dosimetry-based treatments. Statistical analysis was performed by Mann-Withney and Chisquared test, univariate receiver operating characteristics (ROC) analysis, and interpolation of dose–response data by a logistic model. Results. Dosimetric differences between the unhealed and the healed group (p = 0.0067) resulted from the 120 treatments based on absorbed dose prescriptions, also after conversion of the absorbed dose values in BED (p = 0.0049): the Area-under-curve (AUC) was 0.758 and 0.770, respectively. No significant differences were observed for the healing probability between the BED- or absorbed dose-based treatments (p = 0.423). Considering the total 187 dosimetry-based treatments, the absorbed dose/BED-response curves showed regular trends with r-value of 0.979 and 0.977, respectively. The absorbed dose associated to a healing probability of 50% and 95%, was 42.6 Gy and 242.3 Gy, respectively. The probability of recurrence was 9.6%, exactly half of that associated to the empiric treatment group (19.3%, p = 0.0081). Conclusions. Patient-specific dosimetry has proven to increase therapeutic effectiveness, reducing the recurrence frequency and the need of repeated treatments. https://doi.org/10.1016/j.ejmp.2018.04.107
98. Patient-specific estimation of the red marrow extracellular fluid fraction for improving the accuracy of red marrow dosimetry in radioimmunotherpy M. Pacilio a, C. Borrazzo b,c, N. Galea c, C. Basile d, I. Carbone c a Azienda Ospedaliera Universitaria Policlinico Umberto I, Medical Physics Division, Rome, Italy b Sapienza University of Rome, Department of Radiological, Oncological and Pathological Science, Rome, Italy c Sapienza University of Rome, Department of Public Health and Infectious Disease, Rome, Italy d Area Trasformazione Digitale, Agenzia per l’Italia Digitale, Rome, Italy
Purpose. The red marrow (RM) is the dose-limiting organ in radioimmunotherapy. The RM dosimetry is usually calculated by radioactivity concentrations of blood samples: RM kinetics is derived multiplying the blood kinetics by the ‘‘red marrow-to-blood activity concentration ratio” (RMBLR), calculated by patient-specific RM extracellular fluid fraction (RMECFF) and hematocrit (HCT) i.e., RMBLR ¼ RMECFF/(1-HCT) [1]. Preliminarily, the possible use of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI) for estimating the patient-specific RMECFF was here investigated. Methods. 9 patients (5 men, 4 women) studied with CEMRI for cardiac disorders were examined. Pre- and post-contrast T1 mapping by MOLLI (modified Look-Locker inversion-recovery) sequences was performed, and the extracellular volume fraction (ECV) map was calculated by a novel method - based on a Fast Non-linear Least Squares (FNLS) algorithm. The mean ECV of the spongiosa volume (SV) inside the dorsal vertebra at the heart level was obtained as mean value in a region-of-interest (ROI) lying wholly within the SV. Results. The mean ECV of the SV was (mean[range]): 29.9[24.0– 35.3]%. Considering the ECV as a preliminary estimation of the RMECFF, and accounting also for the patient HCT values (ranging from 0.340 up to 0.499), the mean RMBLR was 0.430[0.316–0.546], in a good agreement with the range of 0.2–0.4 generally reported
in the literature (even though values sometimes well outside this range were also observed) [1]. Conclusion. The CEMRI is accurate and very promising for patient-specific RMECFF estimations. Accuracy improvements by MOLLI sequence optimisation, or correction for the presence of trabecular bone and fatty tissue into the SV, are currently under investigation.
Reference 1. Sgouros G. Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. J Nucl Med 1993;34:689–94. https://doi.org/10.1016/j.ejmp.2018.04.108
99. Absorbed dose correlates with metabolic response to radioembolization of liver metastases with resin 90Ymicrospheres M.E. Ferrari a, F. Botta a, F. Guerriero b, C. Garibaldi a, M. Colandrea a, C.M. Grana a, G. Varano a, G. Bonomo a, F. Orsi a, M. Cremonesi a a b
Istituto Europeo di Oncologia, Milano, Italy Ulss 3 Serenissima, Venezia Mestre, Italy
Purpose. To investigate possible correlation between absorbed dose (AD) and tumour response by means of Tumour Control Probability (TCP) in liver metastases treated with radioembolization (RE) with resin 90Y-microspheres. To assess response, the analysis of parameters from FDG-PET/CT has been preferred to RECIST criteria as metabolic response has proven to anticipate morphologic response. Methods. Patients with chemo-refractory liver metastases from solid tumours scheduled to receive RE underwent FDG-PET/CT scan before and 6 weeks after RE. 99mTc-MAA (75–111 MBq) were injected 2 weeks before RE to perform dosimetry based on SPECT fused to contrast CT. Response assessment was based on PERCIST criteria. Variation (%) of PET parameters versus basal examination were evaluated to establish Complete-Response (CR), Partial-Response (PR), Stable-Disease (SD), Progressive-Disease (PD). Results. 22 patients with hepatic lesions from colon-rectal (11), breast (7), ovary (1), endometrial (1), parotid (1) cancer, cholangiocarcinoma (1) were suitable for analysis. All patients received a single RE treatment (median activity: 1.7 GBq; range: 0.6–2.9 GBq). Median (range) tumour AD: 100(30–443) Gy. Metabolic response rate of lesions based on PERCIST were: CR = 31%; PR = 28%; SD = 24%; PD = 17%. Two different TCP curves were obtained by probit regression when considering: i) endpoint-1: PR or CR; ii) endpoint2: CR only (p < 0.01 in both cases). For tumour AD> = 220 Gy only CR were observed. TCP of 50%, 75%, 100% were obtained at: i) 108, 120, 165 Gy; ii) 135, 160, 225 Gy. Conclusions. Despite the variety of primary tumours, relatively low cohort of patients, and uncertainty of dosimetry with 99mTcMAA, our preliminary data provided evidence of correlation between response based on PET/CT and AD. These encouraging results need to be confirmed with more ample dataset and, possibly, tumour type differentiation. Other PET/CT parameters such as the metabolic tumour volume and tumour lesion glycolysis are being considered for comparison with PERCIST and possible improved correlations. https://doi.org/10.1016/j.ejmp.2018.04.109