Linearity in dose response of PRESAGE dosimeter

Dose response linearity of PRESAGE® dosimeter has been confirmed in the previously published studies. ^{Reference Zhao, Newton, Oldham, Das, Cheng and Adamovics31–Reference Abdul Rahman, Bräuer-Krisch and Brochard33} In accordance with the investigation by Iqbal et al., breast-shaped anthropomorphic PRESAGE® dosimeter with EBT2 films inserted was irradiated with 6 MV beam with the 5-field IMRT plan. PRESAGE® had Z _eff and physical density of 7·6 and 1·07 g/cm³, respectively. It was scanned with Duke midsized optical scanner dedicated for RPC (Duke University, Durham, NC, USA). ^{Reference Newton, Thomas, Ibbott and Oldham21} OP-CT scans of PRESAGE® did not give rise to any variation in the OD of the PRESAGE®. In Figure 1, the radiochromic response was found linear showing sensitivity of 0·0059 OD change for a path length of 1 mm. PRESAGE® dosimeter showed a coefficient of variation of 1·0%. EBT2 had 0·75% coefficient of variation. ^{Reference Iqbal, Gifford, Ibbott, Grant and Buzdar23}

Figure 1. OD to dose curve for PRESAGE (a); OD to dose curve for EBT2 film (b).

Further studies by Iqbal et al. on brachytherapy, there appeared an uncertainty of 0·8% in OD, estimated for breast-shaped PRESAGE® dosimeter and 0·7% for EBT2 film. A Strut-Adjusted Volume Implant (SAVI) device was used for irradiating the PRESAGE® dosimeter. While calibrating PRESAGE®, radiation dose was delivered to the small volumes from the same batch of breast-shaped PRESAGE® with an intent to detect errors when comparing dose distribution. ^{Reference Aland, Karin and Kenny34,Reference MacDougall, Miquel and Keevil35} The volume effect uncertainty of PRESAGE® necessitates the utilisation of normalisation as to compare dose distribution of PRESAGE® with Oncentra TPS and EBT2 film. ^{Reference Iqbal, Ibbott, Lafratta, Gifford, Akram and Buzdar36}

For the two film planes, the maximum dose difference between PRESAGE® and Oncentra TPS was 4·5% and between Oncentra TPS and EBT2 film was 2·42%. Further, mean percentage differences of skin dose between PRESAGE® and Oncentra TPS were 3·54 and 2·85% for films 1 and 2, respectively. At various chosen number of points, mean percentage differences between Oncentra and EBT2 film were 0·97 and 0·53% for films 1 and 2, respectively (Figure 2).

Figure 2. (a) Comparison of the calculated and measured point skin doses for PRESAGE, Oncentra Brachy Planning TPS (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden) and EBT2 film for film 1. (b) Comparison of the calculated and measured point skin doses for PRESAGE, Oncentra Brachy Planning TPS and EBT2 film for surface film 2.

In 3D conformal radiotherapy, radio-chromic response of an EBT2 film was linear with sensitivity of 0·0057OD variation for a path length of 1 mm. The uncertainty in the net OD was 1·8% in case of EBT2 films with a reference dose of 3 Gy. The sources of errors responsible for introducing uncertainty in OD have been discussed in detail in the literature [3-field]. In the case of PRESAGE®, there was an uncertainty of 0·8% for the same reference dose. The power of dose–response linearity of PRESAGE® did not cause any limitation on the data analysis. ^{Reference Iqbal, Ibbott, Grant, Gifford and Buzdar37}

According to the exploration of Gye Won Choi in MRgRT, dose response curve of EBT3 film illustrated the difference of less than 2% in net OD between the two cases of 0 magnetic field and when adjusted to 1·5 T. ^{Reference Choi38} The performance of PRESAGE® was evaluated by establishing EBT3 film as a standard. PRESAGE® curve displayed under dose response of 9% in the presence of 1·5 T magnetic field. The dose response of PRESAGE® dosimeter showed linearity when used as a relative dosimeter indicating that magnetic field effects would not disturb its dosimetry in this case.

Gamma analysis

Gamma analysis is a well-established verification tool required to compare the agreement between the measured and computed dose distributions. ^{Reference Low, Harms, Mutic and Purdy39} This analysis is essential in evaluating the performance of radiotherapy clinics to deliver the prescribed doses. For research purposes, gamma maps can do an assessment of the efficiency of new dosimeters against standard dosimeters or treatment plans.

Mark Oldham et al. delivered 11-field IMRT plan to the cylindrical PRESAGE® of 16 cm in diameter and 11 cm in height. PRESAGE® measured dose distributions were compared with EBT and Eclipse TPS (Varian Medical Systems, Palo Alto, CA, USA) calculated distributions. Isodose line profiles, gamma maps and DVHs were employed to evaluate the agreement among three dose distributions. ^{Reference Oldham, Sakhalkar, Guo and Adamovics40} A good agreement was found with a maximum difference of 3% among them at all points excluding within 3 mm outer ring due to edge artefacts. Gamma pass ratio was 96% between the Eclipse and PRESAGE® measured dose distributions. Guo et al. evaluated the functionality of PRESAGE for 5-field radiotherapy by comparing the agreement among the Eclipse TPS calculated, PRESAGE® and EBT film measured dose distributions. The gamma criteria of 4% dose difference and 4 mm distance to agreement (DTA) appeared. Owing to the presence of edge artefacts, the outer layer comprising 10% of the radius of PRESAGE® dosimeter was not included. ^{Reference Guo, Adamovics and Oldham41} From the investigation by Oldham et al., gamma criteria of 3%/3 mm occurred with a pass rate of 96% for Eclipse TPS versus PRESAGE® dosimeter without considering edge artefacts in 11-field IMRT. Even taking into account the region of edge artefact, PRESAGE® dosimetric characteristics showed similarity with that of film dosimeters. The gamma pass rates for PRESAGE® versus Eclipse and EBT film versus Eclipse were 91·4 and 94%, respectively. ^{Reference Oldham, Sakhalkar, Guo and Adamovics42} Sakhalkar et al. achieved a good agreement among EBT film, PRESAGE® and Eclipse TPS with passing rate of more than 98% using head and neck phantom in IMRT. This analysis had a gamma criteria of 4%/3 mm by excluding 4 mm outer rim of the PRESAGE® due to edge artefacts. ^{Reference Sakhalkar, Adamovics, Ibbott and Oldham43} Thomas and Newton et al. achieved a gamma criteria of 3%/3 mm with 97·9% passing rate for PRESAGE® versus TPS in 4-field IMRT. ^{Reference Thomas, Newton, Adamovics and Oldham44} Moutsatsos et al. employed PRESAGE® dosimeter for verifying dose distribution generated in helical tomotherapy using small fields for head and neck treatment plans. A comparison was made among TPS calculated, PRESAGE® and film measured dosimetry results. Gamma index pass rates were achieved more than 90% and uncertainties remained within 2%. ^{Reference Moutsatsos, Pantelis and Antypas45}

Iqbal et al., for 2D axial gamma comparison, determined the pass rates of 91·2, 90·6 and 88·4% for EBT2 versus Pinnacle, PRESAGE® versus Pinnacle and EBT2 versus PRESAGE®, respectively, in breast IMRT. ^{Reference Iqbal, Gifford, Ibbott, Grant and Buzdar23} In all comparisons, failures were found near the dosimeter periphery in the 8 mm outer layer of the PRESAGE®. In this area, PRESAGE® measured doses are possibly imprecise owing to edge artefacts, and Pinnacle determined doses are likely to be erroneous due to complexity in modelling the buildup region. Without this 8 mm outer layer, gamma pass rates increase to 95% for PRESAGE® versus Pinnacle comparison (Figure 3).

Figure 3. Gamma maps (a) (±3%/3 mm) between Pinnacle, EBT2 and PRESAGE for a region of PTV 5 mm on film plane; (b) (±3%/3 mm) in the transverse and sagittal planes for PTV 5 mm intersecting film plane.

DVH analysis

From studies by Iqbal et al., in 5-field breast IMRT plan, DVHs of the planning target volume (PTV) determined by PRESAGE® were different from that calculated by the Pinnacle TPS (Philips Radiation Oncology Systems, Fitchburg, WI, USA). ^{Reference Iqbal, Gifford, Ibbott, Grant and Buzdar23} In addition to this, a slightly less homogeneity was observed in PRESAGE® determined DVH than that calculated by Pinnacle TPS. This is due to aberrations occurring at the edges of the breast-shaped PRESAGE®. A maximum dose difference of 5% for the PTV DVH was seen at 5 and 95% of the fractional volume. For PTV 1 mm, PTV 3 mm and PTV 5mm, sub-volume DVHs showed a maximum dose difference of 3, 2 and 1%, respectively. DVH of the breast-shaped PRESAGE showed a deviation from Pinnacle calculated DVH occurring between 0·5 and 3 Gy dose. Edge artefacts are responsible for this discrepancy because the breast region of interest encircles the whole PRESAGE.

Comparison between isodose line profiles of PRESAGE, TPS and EBT film

In IMRT by Iqbal et al., Pinnacle TPS computed, PRESAGE® and EBT2 film measured line dose distribution gave a good agreement among them with a maximum dose difference of 5% which occurs at the periphery of the breast. ^{Reference Iqbal, Gifford, Ibbott, Grant and Buzdar23} However, it is complicated to investigate about the dose distribution of which dosimeter (PRESAGE® and EBT) correlates more with Pinnacle calculated distribution. Moreover, within 80% of the central field width, a maximum difference of 2% was produced among three line dose distributions. PRESAGE® and EBT2 film measured dose distributions are related to two independent deliveries of the same radiotherapy plan. Line profiles are presented in Figure 4.

Figure 4. Line profiles of Pinnacle, PRESAGE and EBT2 film dose distributions from axial slices.

Verification through dose profiles

In 2010, Pierquet et al. determined a satisfactory agreement between PRESAGE® measured and Eclipse calculated isodose line profiles in brachytherapy. PRESAGE® dosimeter with Z _eff of 8·1 was irradiated with 7 Gy dose at 1·5 cm from the centre of the source, and line dose distributions were obtained along the transverse axis from the planes. Edge artefacts were present in the ± 3 mm region from the source centre, but on the whole measured and calculated dose distributed agreed well with each other in the region between 5 and 20 mm from the source centre. ^{Reference Pierquet, Craciunescu, Steffey, Song and Oldham46} In the studies by Iqbal et al. in 2018, for taking measurements of isodose profiles, PRESAGE® was cut at its central long axis and EBT2 film pieces were inserted between the two halves of the PRESAGE. The maximum dose difference in dose profiles was 2·48% between Oncentra TPS and PRESAGE® using both films. Between EBT2 film and Oncentra TPS, the maximum difference was 4·06%. The mean dose differences in the line plots of both films 1 and 2 were 2·25 and 1·80% between Oncentra and PRESAGE® and 3·31 and 2·82% between Oncentra and EBT2 film. ^{Reference Iqbal, Ibbott, Lafratta, Gifford, Akram and Buzdar36}

DVH of PTV and normal tissue

Iqbal et al. in their studies showed a DVH comparison between Oncentra TPS and PRESAGE® which showed a maximum percentage difference of 4%. This difference occurred because of the reflection artefacts as described in previous studies. ^{Reference Guo, Adamovics and Oldham11} The PTV_EVAL V90 and V95 of breast-shaped PRESAGE® and Oncentra were 97, 96·59% and 99·6, 98·95%, respectively.

The dose distribution determined by the PRESAGE® varied from Oncentra calculated dose distribution particularly near the edges of the dosimeter due to edge artefacts in the PRESAGE® dose distribution. By considering DVH curve of PTV_OPT, PRESAGE®, measured dose distribution was found insignificantly less homogeneous than Oncentra calculated dose distribution because of the presence of small regions of relatively under and over lying closer to the dosimeter edges. A maximum dose difference of 4% appeared at the lower and upper volume ends. From the DVHs of 1, 3 and 5 mm sub-volumes of the normal breast tissue, the maximum dose difference of 3·2, 2·5 and 1·5% occurred between the PRESAGE® and Oncentra treatment plans.

DVHs comparison between PRESAGE and Pinnacle TPS

DVH curve of the PRESAGE® PTV showed less homogeneous dose distribution than Pinnacle calculated dose distribution with a maximum dose difference of 2·2%. Furthermore, gross tumor volume (GTV) and clinical target volume (CTV) manifested 0·8 and 1·5% dose difference. This difference again happened due to edge artefacts similar to that in other treatment techniques (IMRT and brachytherapy) (Figure 6).

Figure 6. GTV, CTV and PTV DVH comparison between the PRESAGE® and Pinnacle3 Planning dose distributions.

Edge artefacts

Dose distribution measurements with PRESAGE®/OP-CT often undergo deterioration due to edge artefacts. This effect has been reported in detail in the literature by Doran et al. ^{Reference Doran and Yatigammana47} The sensitivity of PRESAGE® is highly affected by any mismatch in the refractive indices between the matching fluid and the dosimeter such that the mismatch of only 0·3% can produce the edge artefact of several millimeters. In the studies involving PRESAGE®/OP-CT dosimetry, edge artefacts regions have been excluded which extend from the outer 3 to 8 mm rim of the PRESAGE dosimeter. ^{Reference Oldham, Sakhalkar, Guo and Adamovics48,Reference Thomas, Newton, Adamovics and Oldham49}

Dosimeters response in magnetic field

For the measurement of dose distribution in magnetic field, the response of various dosimeters was investigated. Meijsing et al. determined that by changing the strength of magnetic field from 0 to 1·2 T, the response of farmer-type ionisation chamber varies by 10–15%. ^{Reference Meijsing, Raaymakers and Raaijmakers52} Conventional 2D dosimeters like thermo luminescent dosimeters (TLDs), optically stimulated luminescent dosimeters OSLD and EBT3 film were not affected by magnetic field, but dosimetric results with PRESAGE showed an under dose response. ^{Reference Mathis, Sawakuchi and Flint53–Reference Zhao, Newton, Oldham, Das, Cheng and Adamovics57}

Validity of PRESAGE dosimeter in MRgRT

Gye Won Choi demonstrated the viability of employing PRESAGE® dosimeters in MRgRT. In this treatment modality, PRESAGE® cuvettes (1 cm x 1 cm x × 4 cm) were irradiated with 1, 4, 7 and 10 k MU by adjusting magnetic field to 1·5 T. From the studies by Mathic et al., magnetic field did not produce any considerable effect on the EBT3 film response, so it was chosen as the standard for the verification of the PRESAGE® dosimeter in this modality. ^{Reference Mathis, Sawakuchi and Flint53} EBT3 and the PRESAGE® measured dose distributions when compared with each other showed a gamma criteria of 5%/3 mm. Despite the modifications in dose distributions caused by ERE, there observed still a satisfactory agreement between EBT3 and PRESAGE® measured doses with passing rate of more than 90%. ^{Reference Choi38}

In the radiotherapy techniques currently in use, all the differences among the EBT, PRESAGE measured and TPS calculated doses were found within the tolerance limits of ±5% specified by ICRU and also in the literature. ^{54–Reference Shamsi, Buzdar, Atiq, Atiq, Altaf and Iqbal56}