Radiation Protection in BNCT Patients

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1 Radiation Protection in BNCT Patients J. Kessler 2, H. Blaumann 1, D. Feld 2,, E. Scharnichia 1, I. Levanón 1, C. Fernández 1, G. Facchini 1, M. Casal 3, S. González 2, J. Longhino 1, O. Calzetta 1, B. Roth 3, P. Menéndez 3, S. Liberman 2, M. D. Pereira 4 1 Centro Atómico Bariloche, Comisión Nacional de Energía Atómica, Avda Bustillo 9500, S. C. de Bariloche, 8400 Río Negro, Argentina 2 Centro Atómico Constituyentes, Comisión Nacional de Energía Atómica, Avda General Paz 1499, San Martin, B1650KNA Provincia de Buenos Aires, Argentina 3 Instituto de Oncología Ángel Roffo, Avda San Martín 5481, 1417, Ciudad Autónoma de Buenos Aires, Argentina 4 Agencia Nacional de Promoción Científica y Tecnológica, Av. Córdoba 831, Ciudad Autónoma de Buenos Aires, Argentina Abstract. Boron Neutron Capture Therapy (BNCT) is a technique that selectively targets cancer cells while sparing normal tissues by virtue of the differential uptake of a 10 B carrier compound in tumor. The National Atomic Energy Commission (CNEA) and the Oncology Institute Angel H. Roffo (IOAR) began a BNCT programme in 2003 for treating cutaneous skin melanomas in extremities. The neutron beam used is the hyperthermal one developed at the RA-6 Reactor of the Bariloche Atomic Centre (CAB). The prescribed dose is delivered in one fraction and therefore patient positioning and knowledge of the dose received by normal tissue are crucial. 10 irradiations have been done since The dose prescription was determined by the maximum tolerable skin dose. Due to the characteristics of this treatment the patient body might be exposed both to the primary beam and to the secondary photon beam produced by neutron capture at the target itself. A patient radiation-monitoring plan was implemented in order to evaluate the gamma dose delivered to sensible organs of each patient. An acrylic water-filled whole body phantom was used for preliminary gamma dose and thermal neutron flux measurements at positions related to patient s body sensible organs considering tentative patient positions. The beam port shielding was, in this way, optimized. TLD-700 and Manganese foils were used for gamma and thermal neutron detection. The TLD-700 thermal neutron response was previously evaluated with the in-phantom beam dosimetry characterization. In-vivo dosimetry with Thermal Luminescent Dosimeters (TLD) is implemented in order to evaluate gamma dose to sensible organs of each patient. These organs are chosen depending on its distance from the zone to be irradiated and its radio-sensibility. TLD s have been positioned outside the irradiated area. Maximum gamma dose received outside the radiation field in healthy tissues was well below tolerance dose for the compromised organs. KEYWORDS: BNCT, TLD, tolerance dose, positioning 1. Introduction BNCT is a radiation selective technique which uses a neutron beam impinging over cells containing a 10 B compound, boronophenylalanine (BPA) in this case, which is infused intravenously before the beginning of irradiation. The beam contains neutrons as well as photons which have to be taken into account for radiation protection. The BPA distinguishes between normal and tumor cells and mainly selects the latter ones. The reaction 10 B(n, α) 7 Li produces an α (alpha) particle and a 7 Li recoil nucleus of high Linear Energy Transfer (LET) and very short range in tissue, as well as an associated photon with an energy of MeV. The former particles are the responsible of the very high dose absorbed by tumor cells, while normal cells receive a considerably lower dose. The CNEA and the IOAR outlined a protocol for the treatment of metastatic melanomas in extremities. This type of skin melanoma is a highly lethal disease for which most of the adjuvant treatments have failed [1]. BNCT treatments began in Argentina in 2003 using the RA-6 reactor belonging to the CNEA and located in Bariloche. Since then, 7 patients with multiple subcutaneous skin metastases of melanoma have been treated and 10 irradiations have been carried out. As the beam is a mixed one, neutron as well as gamma doses to normal tissue have to be known for protection purposes. The outcome concerning gamma dose to normal tissue measured in patients, is presented in this paper. 1

$Dose prescription is done taking into account the maximum tolerable dose in normal skin for a single and unique fraction, and the values ranged from 16.5 to 24 Gy-Eq [2].$

2 2. Material and Methods The whole dose is delivered in one session for each field and the patient is treated through a unique entrance port of 15 cm diameter (Fig. 1). Dose prescription is done taking into account the maximum tolerable dose in normal skin for a single and unique fraction, and the values ranged from 16.5 to 24 Gy-Eq [2]. Figure 1: Schematic representation of the BNCT facility showing the main components of the beam port 2.1 Beam characteristics The RA-6 is a pool type reactor with 500 kw of nominal power. The original epithermal beam was thermalized for the treatment of superficial tumors, being now a hyperthermal mixed beam containing neutrons of lower energy getting the maximum flux between 0.5 cm and 1.0 cm depth in water. Fig. 1 shows a schematic representation of the port and its main components [3]. Dosimetric distribution of gamma dose has been done in a body-shaped water phantom using TLD 700 distributed in 16 different points of the phantom, simulating several regions of the body. The thermal neutron flux has been estimated with Mn foils [4]. 2.2 Patient positioning The main difference between traditional Radiotherapy and this modality is that the port of the reactor is stationary and cannot be rotated around the patient like the gantry of a typical external beam machine as a linear accelerator or a Co-60 unit. Thus, the positioning of patient is highly complicated, the resulting positions being sometimes a little uncomfortable (Fig. 2). 2

Figure 2 a) Positioning scheme b) Irradiation region of patient Nº 6 for patient Nº 6 The patient position is

Treatment Room (TR) in Bariloche (Fig. 3).

Moreover, the window of the Simulation Room has a beam s-eye view as it is made of transparent acrylic (Fig. 4).

report in order to reproduce the positioning at the TR, where there isn t a beam s eye view.

3 Figure 2 a) Positioning scheme b) Irradiation region of patient Nº 6 for patient Nº 6 The patient position is simulated at the Simulation Room (SR) in Buenos Aires using immobilisation devices which are afterwards taken to the Treatment Room (TR) in Bariloche (Fig. 3). The Simulation Room and the Treatment Room both have identical gridded windows. Moreover, the window of the Simulation Room has a beam s-eye view as it is made of transparent acrylic (Fig. 4). All the anatomical marks are photographed at the SR and patient position coordinates registered in a simulation report in order to reproduce the positioning at the TR, where there isn t a beam s eye view. The position is repeated and verified at the TR one day before treatment. Immobilisation is crucial for these treatments as the irradiation times are about 60 minutes. Figure 3: Treatment Room showing the port Figure 4: The beam s eye view at the Simulation Room 3

2.3 Patient irradiation and in-vivo dosimetry Patients are infused intravenously over 90 minutes, blood samples are extracted in spans of 10 15 minutes during this period and until the beginning of

4 2.3 Patient irradiation and in-vivo dosimetry Patients are infused intravenously over 90 minutes, blood samples are extracted in spans of minutes during this period and until the beginning of irradiation, in order to analyze blood boron concentration. Those values are plotted versus time and fitted with an open two-compartiment pharmaco kinetic model for getting the final irradiation time [5]. After infusion patient is carefully positioned at the TR following the simulation report. Marks are added on the patient for monitoring patient movement from outside through a video camera during the irradiation (Fig. 5). Figure 5: Record of patient position at the beginning and end of treatment. LiF (TLD) is commonly used for in vivo dosimetry in other radiotherapy modalities. Furthermore, the use of TLD-700 in a mixed neutron-photon beam is reported and their accuracy is well determined [6],[7]. For each irradiation field, between 5 and 7 TLD s 700 are distributed over the patient, outside the irradiation area (Fig. 6) in order to estimate the gamma dose received by healthy tissues. The position of TLD s is chosen according to the localisation of each tumor and the type of organs at risk (OR) at the surroundings of the irradiated region. It is worth while to emphasize that staff remains in a controlled area during the irradiation and they don t enter to the TR till the dose rate is below 0.20 msv/h. Dose values read from personal dosimeters have been always below 0.15 msv. 4

Figure 6: TLD localisation for patient Nº3 for fields 3 (Fig.6 a), 2 (Fig. 6b) and 1 (Fig.

whose schedule included 3 irradiation fields.

TLD s positions for each field are shown in Fig. 6.

5 Figure 6: TLD localisation for patient Nº3 for fields 3 (Fig.6 a), 2 (Fig. 6b) and 1 (Fig. 6c) a) b) TLD c) TLD As an example, we illustrate the particular case of patient Nº 3 whose schedule included 3 irradiation fields. The treated regions (the calf and the heel of right leg and the right foot sole) and the TLD s positions for each field are shown in Fig. 6. For one patient a protective borated polyethylene block was needed in order to avoid high neutron doses to parts of the body which were at the same level of the port (Fig.7). 5

6 Fig. 7: Patient Nº 2 with the shielding block Shielding block 3. Results An excellent reproduction of patient positioning is achieved and the monitoring showed that patient movement provoked a shift of only 2 to 4 mm of the irradiated region. This shift produces an estimated change in thermal neutron flux of 5%. The dose values got from the TLD s for the patient taken as example are shown in Table 1. As it was previously stated, the thermal neutron dose is reported to be 10% [4] to 20% [7], and these values are comparable to the uncertainty in the estimation of gamma dose. The contribution from thermal neutron field to TLD s is included and so, the values in Table 1 give higher dose levels than the actual absorbed gamma dose in inner organs at risk by a factor of 2.3 [4], so they can be considered a conservative estimate of dose. Measurements performed by Blaumann in the anthropomorphic water filled acrylic phantom [4] showed that outside the irradiated area, neutron dose was of the same order of magnitude than the uncertainty in the determination of gamma dose, thus it can be neglected. Based on these results, it was considered that doses in organs at risk outside the irradiated zone were due mainly to gamma rays, and TLD 700 were used to estimate it. The OR for all cases were both lungs and bladder and TLD s have been placed near them. The rest of TLD s locations have been chosen according to their proximity to the port. In patient 3, left knee and abdomen were near the port for all fields, so TLD s have been positioned there. For field 1 (right calf) the left groin was measured because it was near to the ovaries, for field 2 (right heel), the forehead and the eyes because they were facing the port, and for field 3 (right foot sole) again because the forehead was facing the port and the left foot was near the port. For all patients, doses have been well below 1Gy. This result also includes the estimations for the patient who had the protective block. 6

7 Table 1: Gamma dose from TLDs vs. body region for the field Nº 1 of patient Nº 3 Field Localisation Doses [cgy] Left groin Right Calf 2 Right Heel 3 Right Foot Sole Abdomen 8.6 Left knee 16.1 Right lung 7.9 Left lung 3.8 Bladder 11.4 Forehead 7.2 Abdomen 6.9 Left knee 10.7 Right lung 6.3 Left lung 6.2 Bladder 6.2 Forehead 7.7 Abdomen 9.4 Left knee 15.7 Right lung 8.3 Left lung 8.1 Bladder 10.3 Left foot Conclusion In spite of the uncomfortable position, the movement of the irradiated zone during irradiation was only of 2 to 4 mm and it is perfectly acceptable as it is the similar tolerable displacement in others radiotherapy modalities. The beam port shielding proved to be effective for patient radiation protection according to the results of the TLD s doses. Maximum dose received outside the radiation field in healthy tissues was well below tolerance dose for the sites measured. TLD s proved to be a useful tool to estimate doses in OR for this kind of treatments. The video system to monitor patietnts during irradiation is useful to determine their movements, and also provides sufficient data to calculate the retrospective dose distribution when needed. The general BNCT procedure resulted safe from the radiation protection point of view. REFERENCES [1] PAWLIK, T.M., SONDAK, V.K. Malignant melanoma: current state of primary and adjuvant treatment Crit. Rev. Oncol. Hemat. (2003) 45(3), [2] ROTH, B.M, et al. BNCT Clinical trials of Skin Melanoma Patients in Argentina 1st Congress of the Latin American of the Oncological Radiation Therapy Association, Montevideo, Uruguay (2007) [3] BLAUMANN, H.R., et al. Boron neutron capture therapy of skin melanomas at the RA-6 reactor. A procedural approach to beam set up and performance evaluation for upcoming clinical trials, Med. Phys. (2004) 31(1), [4] BLAUMANN, H., Evaluación de la distribución de dosis gamma en un fantoma cuerpo entero en la facilidad de BNCT del reactor RA-6, Informe técnico CNEA-CAB 47/014/02 (in Spanish) 7

8 [5] GONZÁLEZ, S.J., et al. First BNCT treatment of a skin melanoma in Argentina: Dosimetric Analysis and clinical outcome, Applied Radiation and Isotopes, (2004) 61, [6] KRY, S. F. et al: The use of LiF(TLD-100) as an out-of-field dosimeter, J. Appl. Clinical Medical Physics, (2007), 8 (4) [7] CARITA ASCHAN, Applicability of thermoluminiscent dosimeters in X-Ray organ dose determination and in the dosimetry of systemic and boron neutron capture radiotherapy University of Helsinki, 1999, Report Series in Physics, HU-P-D77, ISSN , ISBN

Single Photon Emission Tomography Approach for Online Patient Dose Assessment in Boron Neutron Capture Therapy

Single Photon Emission Tomography Approach for Online Patient Dose Assessment in Boron Neutron Capture Therapy Daniel M Minsky a,b,c*, Alejandro Valda a,b, Andrés J Kreiner a,b,c and Alejandro A Burlon