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Remarks on reporting and recording consistent with the ICRU Reference Dose

Remarks on reporting and recording consistent with the ICRU Reference Dose Background: ICRU 50/62 provides a framework to facilitate the reporting of external beam radiotherapy treatments from different institutions. A predominant role is played by points that represent "the PTV dose". However, for new techniques like Intensity Modulated Radiotherapy (IMRT) - especially step and shoot IMRT - it is difficult to define a point whose dose can be called "characteristic" of the PTV dose distribution. Therefore different volume based methods of reporting of the prescribed dose are in use worldwide. Several of them were compared regarding their usability for IMRT and compatibility with the ICRU Reference Point dose for conformal radiotherapy (CRT) in this study. Methods: The dose distributions of 45 arbitrarily chosen volumes treated by CRT plans and 57 volumes treated by IMRT plans were used for comparison. Some of the IMRT methods distinguish the planning target volume (PTV) and its central part PTV (PTV minus a margin region of × mm). The reporting of dose prescriptions based on mean and median doses together with the dose to 95% of the considered volume (D ) were compared with each other and in respect of a prescription report with the aid of one or several possible ICRU Reference Points. The correlation between all methods was determined using the standard deviation of the ratio of all possible pairs of prescription reports. In addition the effects of boluses and the characteristics of simultaneous integrated boosts (SIB) were examined. Results: Two types of methods result in a high degree of consistency with the hitherto valid ICRU dose reporting concept: the median dose of the PTV and the mean dose to the central part of the PTV (PTV ). The latter is similar to the CTV, if no nested PTVs are used and no patient model surfaces are involved. A reporting of dose prescription using the CTV mean dose tends to overestimate the plateau doses of the lower dose plateaus of SIB plans. PTV provides the possibility to approach biological effects using the standard deviation of the dose within this volume. Conclusion: The authors advocate reporting the PTV median dose or preferably the mean dose of the central dose plateau PTV as a potential replacement or successor of the ICRU Reference Dose - both usable for CRT and IMRT. Page 1 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 IMRT-plans. Additionally, simultaneous integrated boost Background ICRU 50 and ICRU 62 provide a framework which struc- (SIB) IMRT cases were considered, in which nested dose tures the reporting of external beam radiotherapy treat- plateaus are formed [10]. To describe the dose to a plateau ments from different institutions [1,2]. These reports refer and to exclude effects of a dose gradient at the border of to conventional conformal radiation techniques (CRT). each volume, the authors preferred to define volumes that Within that framework, the definition of points that rep- are distant to each other. This condition cannot be ful- resent "the PTV dose", "prescription dose" or "intended filled by the clinical target volume (CTV) in the cases of dose" plays a predominant role. SIB. Since then, new techniques like Intensity modulated radi- Methods otherapy (IMRT) have been introduced. Early IMRT could In this retrospective study, treatment planning was per- only create more inhomogeneous dose distributions, as it formed on a Philips Pinnacle3™ version 8.0 m planning was shown by Bratengeier et al. for head and neck studies system (Philips Radiation Oncology Systems, Fitchburg, [3]. Even if today IMRT can be planned more homogene- Wi, USA). Siemens Primus™ (Siemens Healthcare, Erlan- ously, the positioning of a point whose dose can be called gen, Germany) and Elekta Synergy™ (with BeamModula- "characteristic" of the planning target volume (PTV) is tor™; Elekta AB, Stockholm, Sweden) linacs were regarded as difficult, if not ambiguous. Therefore the def- commissioned with 10 mm or 4 mm leaf width (in the inition of the ICRU Reference Point has become problem- isocentre), respectively. The CT slice distance was 3 or 5 atic. Previous work like that of Kukolowicz et al. has to be mm. A dose grid size of between 2 and 4 mm was chosen. revised for application to IMRT [4]. As a result of the loss The step and shoot IMRT plans are optimised by the Ray- of significance of the ICRU Reference Point, a plurality of search™ direct machine parameter optimisation (DMPO) volume based dose concepts are currently contending, module, a direct aperture optimisation (DAO) method such as the mean dose to the PTV (PTV D ) and the [11]. Not more than 50 segments per plan were used. mean clinical target volume CTV (CTV D ), the dose to 95% IMRT plans were irradiated with 7, or (mostly) 9 equidis- mean of the PTV (PTV D ) and others [5-7]. The IMRT Collab- tant beams or 10 non-equidistant fields (breast cases) orative Working Group recommended the reporting of [12]. The dose distribution was calculated using a col- "Prescribed (intended) dose, as well as the point or vol- lapsed cone algorithm. ume to which it is prescribed; ....Dose that covers 95% (D95) of the PTV and CTV. Dose that covers 100% The patient data were randomly selected from the normal (D100) of the PTV and CTV (i.e., the minimal dose). clinical routine. 70 patients with different tumour locali- Mean and maximal doses within the PTV and CTV. Per- sations and a total of 102 treatment plans were examined. centage of the PTV and CTV that received the prescribed 12 plans resulted from technique changes; 24 plan vari- dose (V100)...." [8]. A recent ASTRO recommendation ants resulted from the application or removal of a bolus. added some further details to be recorded - i.e. D , D , For CRT 38 patients with several localizations were cho- mean 0 D , D , V in PTV and CTV additional to the "pre- sen (i.e. 10 head and neck cases, 9 tumours of the abdo- 95 100 100 scribed dose" [9]. men, 7 breast patients with 2 plan each, 4 metastases). 37 patient models with 57 target volumes were used for IMRT Often the PTV D is used as prescribed dose because it is techniques (i.e. 19 head and neck patients, 10 breast supposed to be a dose prescription regarding biological patients). 6 MV photons were applied for breast, head and aspects [7]. This is popular in studies of the Radiation neck tumours, 10 MV or 18 MV for the tumours of the ® ® Therapy Oncology Group (RTOG ), i.e. the protocols abdomen. 0022, 0522, 0615, 0619. This procedure differs from the Volume definitions and methods of dose prescription and ICRU Reference Dose concept and the correlation of these two concepts is unclear. reporting All volumes came from clinical practice and were ran- For that reason, the authors examined different volume domly selected. Only one planning target volume was based definitions. In particular, their consistency with the changed for the sake of this study. In addition to the clin- currently valid "ICRU Reference Dose" (ICRU RD, the ical target volume (CTV) and the planning target volume dose at the ICRU Reference Point) is investigated. In par- PTV we defined a "PTV " in which the volume is shrunk by ticular the ratio of the dose defined by several possible an amount × mm, and maintains a distance of × mm ICRU Reference Points and the dose defined by the differ- towards air. It should be noted that for SIB the nested ent reporting procedures is investigated for the same plan. PTVs abut each other. PTV then excludes the high dose Moreover, the correlation of the pairwise application is area just as the low dose areas of the PTV. This volume is explored by calculating the standard deviation of these designated as the "central target volume". It is used to ratios for all plans and target volumes. Definitions are describe the plateau dose. It comprises, depending on the applied to classical (forward planning) CRT plans and to choice of x, approximately the clinical target volume Page 2 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 (CTV) in the non-SIB cases. Contrary to the CTV it is large lung areas, or if the volumes included mammaria designed to contain all the points that eventually would interna lymph nodes. The mean volume for IMRT breast be allowed to be chosen as ICRU dose prescription points; cases was therefore larger than for CRT. the points from the CTV or PTV from the dose gradient area towards an inner PTV would not comply with that In this study the arithmetic mean and median averages of condition. PTV shells that are generated using a margin of the dose distribution in the PTV and PTV were evaluated. less than 2× around an inner target volume would not In addition D in PTV and PTV were determined. Their 95 5 form a dose plateau and PTV is not defined for the outer relationships were calculated for a plurality of ICRU Ref- PTV ring. This situation will be addressed in the discus- erence Points selected according to ICRU criteria. For the sion section. For this planning study x = 5 mm was conventional plans 236 points were used which were selected, a distance that is frequently chosen to avoid sur- acceptable ICRU reference points, for the IMRT plans 340 face effects [13]. In all conventional cases and 22 IMRT- points. The ICRU Reference Point criteria are: "(1) the cases only one PTV exists. In 15 IMRT-cases 35 nested tar- dose to the point should be clinically relevant; (2) the get volumes were selected and simultaneously irradiated point should be easy to define in a clear and unambigu- (SIB) [10]. The target volumes are fundamentally non- ous way; (3) the point should be selected so that the dose overlapping. Therefore, for SIB they abut one another. The can be accurately determined; (4) the point should be in extension of the volumes is presented in Table 1. a region where there is no steep dose gradient." [2]. The commission added: "These recommendations will be ful- For breast cases, IMRT was only used to replace CRT if the filled if the ICRU reference point is located: - always at the PTV was extremely curved and standard fields included centre (or in a central part) of the PTV,..." Table 1: Overview Non-breast Breast with bolus Breast without bolus CRT IMRT CRT IMRT CRT IMRT Single PTV SIB SIB Central Circumferential PTV PTV n31 47 12 15 20 14 10 14 10 Vol [cm]PTV 837 430 918 124 367 1240 1576 1240 1576 546 471 671 76 212 467 1100 467 1100 PTV 512 202 522 42 127 797 1042 797 1042 383 311 471 37 96 349 823 349 823 σ /D PTV 4.4 3.9 4.0 2.2 5.0 3.9 4.5 7.0 9.0 D mean [%] 2.0 1.8 1.5 0.7 1.7 0.9 1.1 0.9 1.3 PTV 2.3 2.1 2.1 1.6 2.5 2.9 2.8 2.7 3.1 0.7 0.7 0.7 0.6 0.6 0.6 0.7 0.6 0.7 D /D PTV 48.4 51.2 31.1 81.9 40.2 23.7 41.4 0 2.5 min mean [%] 33.7 35.0 37.3 16.7 28.7 24.0 21.7 0 4.2 PTV 85.8 88.3 85.2 95.4 84.7 92.0 85.7 86.6 81.0 10.7 17.6 21.6 1.7 20.6 2.3 7.6 2.3 4.9 D /D PTV 109.6 111.9 109.4 106.9 117.0 111.7 114.3 112.3 116.7 max mean [%] 4.5 6.8 3.2 2.6 7.0 3.0 3.3 3.0 3.0 PTV 108.3 108.4 107.4 104.9 111.8 110.3 112.4 109.6 112.4 4.3 4.5 2.7 2.1 4.5 2.6 3.5 2.6 3.4 n: Number of volumes with related plans. Mean values of Volumes (Vol). Standard deviations of the dose distributions σ , dose minima and maxima (D , D ), divided by the mean doses (D ) within PTVs and PTV shrunk by 5 mm (PTV ) for several groups of plans (CRT: Conformal min max mean 5 radiotherapy, IMRT: Intensity modulated radiotherapy; SIB: Simultaneous Integrated Boost). The upper value in each cell is the mean value; the lower value is the corresponding standard deviation Page 3 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 In almost all cases, four such points are positioned in the the surface on the PTV standard deviation can clearly be central part of each target volume. If possible, one of these seen, whereas the standard deviation of PTV is not points was placed in the centre in the central plane of the affected. For IMRT, the relative standard deviation of the PTV. For IMRT plans with single PTVs, additionally the dose in the PTV (PTV ) was 3.9% (2.1%) for the non- isocentre was chosen as fifth point. The other points were breast plans, 9.0% (3.1%) for the breast plans without arbitrarily placed in areas which seemed homogeneous. bolus and 4.5% (2.8%) for the same plans with bolus The minimum distance between the points was 1 cm, 0.5 (Table 1). This result is similar to that for the CRT-plans, cm for SIB PTVs. The dose to the isocentre and the mean indicating that for step and shoot IMRT using DMPO sim- dose of the other four possible ICRU Reference Points ilar dose homogeneity could be achieved as for the CRT were compared. plans, although the PTV shape was more complex. A detailed view of the IMRT results shows differences for the Furthermore the standard deviations of the doses in the inner PTV (σ = 2.2% (1.6%)) and the annular PTV shells PTV and PTV were determined. Keeping in mind that D (σ = 5.0% (2.5%)). For the latter, the standard deviation 5 0 D (= maximum dose) and D (= minimum dose) can be and hence dose homogeneity suffers especially in the PTV defective, these values are provided as additional informa- from the additional dose gradient towards the inner target tion. volumes. These findings were similar, if CTV was used instead of PTV for nested volumes: the standard deviation Subgroups of patients are created to allow a cross-check of increased by a factor of 1.5, (for 3 of 26 volumes by more the data. than a factor of 2; details see below). Effects of SIB and surface effects The minimum doses for CRT were around 31% (86%) in The characteristics of the 15 head and neck SIB plans were relation to the prescription dose, for IMRT 44% (86%) evaluated. These cases were sorted according to their with large standard deviations of 33% (10%) and 34% topology: The central PTV and the (one or two) circumfer- (16%), respectively. (not shown in the tables). However, ential PTVs. these results can largely be influenced by PTV delineation, surface effects, grid size and dose calculation algorithm. Surface effects at the patient model surface can drastically change even for a slight change of the outline. The behav- The isocentres in the single PTV IMRT cases were used to iour of the different prescription and reporting methods control the adequate setting of the arbitrary chosen ICRU in such situations was investigated by quantifying the reference points. The mean value of their doses differed by effect of the removal of the bolus for configurations which a factor of 0.9995 and the standard deviations were 2.2% were initially planned and optimized with bolus. In clini- and 2.4%, respectively. This indicates a reasonable ICRU cal practice, a bolus can be removed or added according to Reference Point positioning in this work. the skin reaction. The prescription must not change in an Comparison of prescription and reporting methods other way as the dose to the central points in the PTV (just as for ICRU Reference Points). The breast patients were Table 2 correlates some volume based prescription and especially evaluated: Their PTV is near to the patient out- reporting methods and a selection of allowed ICRU Refer- line. Thus they are particularly suited to examine surface ence Points with an ICRU Reference Dose (RD) for non- effects. On the one hand the dose prescription reporting breast plans. The first row of each cell is the ratio of the using the PTV and the PTV were compared. On the other method of a column and to that of a row, averaged over hand the influence of using a bolus of 5 mm thickness all cases. In the second row the respective standard devia- covering the whole breast was tested both for CRT and tion of this average process is presented which indicates IMRT. The bolus was generated by the planning system the dispersion of the data. Ratios of the reported dose for not considering loose contact to the skin as often can be an identical dose distribution can be compared using the observed in clinical practice. Hence, in the breast group upper and the lower part of the table for CRT and IMRT, two extremes are compared, because in clinical practice respectively. ICRU RD (case-mean) is the dose to the neither such a perfect bolus is available nor would the mean value of all chosen examples of an ICRU Reference cases with skin involvement be irradiated without a bolus. Point of each case, finally averaged over all cases. In the right column, ICRU RD, the average of all normalized Results ICRU Dose Points of all cases is presented to show the sta- Plan quality parameters tistical dispersion if different single points are used to rep- The relative standard deviation of the doses in the PTV resent a dose distribution. (PTV , respectively) was 4.4% (2.3%) for the CRT non- breast plans, 7.0% (2.7%) for the breast plans without The standard deviation of the ratio ICRU RD/ICRU RD bolus and 3.9% (2.9%) for the same plans with a bolus (case-mean) - last row, right column - is a measure of the over the whole breast (see also Table 1). The influence of statistical dispersion of the dose at the chosen ICRU Ref- Page 4 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 2: Correlation of prescriptions (non-breast cases) denominator\numerator PTV PTV PTV PTV ICRU ICRU 5 5 D D D D RD RD Mean Mean 95 95 (Case-Mean) [%] [%] [%] [%] [%] [%] CRT PTV D 99.5 100.4 92.4 96.6 99.9 99.9 Median n = 35 0.4 0.6 2.9 1.0 1.4 1.8 PTV D 100.9 92.8 97.1 100.5 100.5 Mean 0.7 2.9 1.2 1.7 2.0 PTV D 92.0 96.2 99.5 99.5 5 Mean 3.1 1.0 1.5 1.8 PTV D 104.7 108.3 108.0 3.1 4.0 4.2 PTV D 103.5 103.4 5 95 1.8 2.1 ICRU RD (Case Mean) 100.0 1.1 IMRT PTV D 100.0 100.5 94.7 97.2 100.3 100.3 Median n = 47 0.8 1.0 2.3 1.5 1.7 2.7 PTV D 100.5 94.7 97.3 100.3 100.4 Mean 1.5 2.4 1.9 2.1 3.0 PTV D 94.3 96.8 99.7 99.7 5 Mean 2.2 1.1 1.3 2.4 PTV D 102.6 107.0 107.0 2.0 2.8 3.5 PTV D 103.0 103.0 5 95 1.8 2.7 ICRU RD (Case Mean) 100.0 2.1 Correlation of several prescription and reporting methods. All methods report for the same dose distribution per study. -- Non-breast cases. The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62 erence Points within a volume, a measure of the correla- ICRU Reference Point was biased by less than 0.6% (when tion among the chosen points. This value should be using all CRT and IMRT plans), whereas the quotient for improved upon by any method which competes with the PTV D was 96% and for PTV D 92%. The D values 5 95 95 95 point based methods. Standard deviations of 1.3% and should be compared with an independent evaluation in 2.3% for the ICRU RD point to point correlations are the author's clinic over 350 patients: there a value of found for all CRT plans and all IMRT plans, respectively 94.3% for a mixture of both PTV groups was achieved. (not shown in the tables). They should also be considered as benchmarks for the correlation of the ICRU RD with A cross-check of dose reporting concepts for the breast any other reporting method: the standard deviations over cases (with bolus; Table 3) and for non-breast, single PTV all plans were 1.5% and 1.4% for PTV D , 1.6% and IMRT (Table 4) reveals almost the same results. Only the 5 mean 1.8% for PTV D , 1.9% and 2.6% for PTV D , 1.7% dose was slightly more homogeneous for single PTV IMRT median mean and 2.2% for PTV D , 4.3% and 5.9% for PTV D (CRT (Table 1). Consequently, the correlation of one ICRU Ref- 5 95 95 and IMRT, respectively). For the first three reporting meth- erence Point with the mean value of all possible ICRU Ref- ods, the average quotient with the reporting using the erence Points expressed by the standard deviation was Page 5 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 2.0% for non breast IMRT in a single PTV (not shown in with patient group characteristics similar to the non- the tables) compared with 2.6% for breast IMRT (Table 3). breast patient group of this work. The prescription dose , D , D and the dose had been correlated with D min max median For non-breast plans the reporting using PTV D , PTV to the isocentre. Except the median dose all parameters median D and PTV D led to comparable results with showed only weak correlation to the prescription dose. mean 5 mean respect to the mean of the ICRU Reference Doses. The These results agree with the results of this work. In Das' larger standard deviations for the ICRU RD reflect the fluc- work, the standard deviation of the ratio of prescription tuation due to the choice of the position of the ICRU Ref- dose and median dose as a measure of the correlation can erence Point. The results for CRT and IMRT are quite be estimated to be between 2% and 3%. In this work, the similar. standard deviation of the ratio ICRU RD (single point) and D was 1.8% for CRT and 2.7% for IMRT plans of median D was not presented in the tables because the standard the non-breast cases (Table 2). The latter value was mainly min deviation of the correlation to other methods was always influenced by SIB cases with onion-skin-like (nested) above 10% for D of PTV and even exceeded 30% for PTVs (3.4%). Otherwise the standard deviation was 2.4% min 5 of PTV. D (single PTV) and 1.6% (central PTV in a SIB constellation min - see Table 4). Thus, the results are similar. Detailed data for subgroups of non-breast IMRT are shown in Table 4. Here 12 patients with a single PTV are Yaparpalvi et al. examined the IMRT plans of 117 patients, differentiated from patients with SIB. For the latter, the 15 some of them with 3 different IMRT plans [7]. They com- central volumes and the 20 circumferential volumes were pared three prescription and reporting methods: the site distinguished. Only volumes with distances of at least 5 specific RTOG guideline, ICRU RD and D . Their mean mm to the patient model outline or plans with boluses results showed a strong correlation of D and ICRU RD mean were considered. with an estimated σ of roughly 2% (from Yaparpalvi Fig. 1) and a much weaker correlation of both with the D , For SIB IMRT, the dose ratio (PTV mean dose) of the D , D -prescriptions of several RTOG protocols. The 5 97 98 outer to the adjacent inner volume was 0.89 (0.82 up to ratio of prescription dose due to the RTOG guidelines and ) and 0.93) for the cases with 2 volumes, 0.87 (0.78 up to 0.92) the ICRU RD was between 103.6% (RTOG 0418, D for cases with 3 nested volumes (outer volume pair) and 105.1% (RTOG 0022, D ); the latter should be compared 0.96 (0.94 ... 0.99) (inner volume pair). Comparing the with the non-breast cases of this work (107.0% for all standard deviations of PTV and CTV for the related outer non-breast IMRT cases; 107.0% and 106.9% for single volumes, the standard deviation of the dose distributions and circumferential volumes, 104.0% for the central vol- increased for the CTV by a factor of 1.49, 1.86 and 1.08, ume of a SIB). They also concluded that the D in the median respectively. The mean dose to the CTV increased with PTV would be a better representation of the ICRU RD than respect of the mean dose to the PTV was by a factor of the D agrees with the results of this work. 5 mean 1.018, 1.019 and 1.005, respectively. Selecting the volume pairs with PTV mean dose differences of more than 9% Several meeting contributions have addressed future (10% up to 22%) between inner and outer PTV, led to ICRU recommendations on dose prescription, recording CTV/PTV dose ratios of 1.029; the ratio of the CTV/PTV and reporting [14,15]: Single point prescription and 5 5 standard deviations was 2.11 (1.68 to 2.89), respectively. reporting will be given up in favour of volume based methods. It was announced that the median dose would Table 3 presents the planning results of the breast cases play a prominent role. This is supported by this work, (CRT: 14 cases; IMRT: 10 cases). The upper part comprises although PTV could be a concept of more biological rele- the cases with 5 mm boluses, whereas the lower part rep- vance, in combination with the related standard deviation resents the same cases without a bolus. This table demon- in this volume (see below). strates the effect of the extended near-surface areas as typical for breast patients (the PTV is delineated approach- The use of PTV D ing the patient outline). Similar results were achieved if The use of D as a substitute or successor for the ICRU RD the bolus for five non-breast cases was removed (not would lead to a conversion factor of typical 1.08 ± 0.04 shown here, see Fig. 1). between PTV D and ICRU RD (non-breast plans, Table 2). Such a factor ought to be considered, if the prescrip- Discussion tion specification is changed. i.e. using PTV D instead of Comparison with other published results PTV D without adequate correction of the prescribed mean Das et al. compared the IMRT practice of five institutions dose would lead to a dose escalation. However, because of with differing planning systems [5]. 803 brain, head and the weakness of the correlation - expressed by the stand- neck and prostate cancer patient plans were evaluated, ard deviation of 2.8 to 4% (see Fig. 2) - such a transforma- Page 6 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 3: Correlation of prescriptions (breast cases -- surface effects) denominator\numerator PTV PTV PTV PTV ICRU ICRU 5 5 D D D D RD RD Mean Mean 95 95 (Case Mean) [%] [%] [%] [%] [%] [%] with bolus CRT PTV D 99.9 100.0 94.1 95.5 98.5 98.5 Median n = 14 0.3 0.4 1.5 1.4 1.5 1.9 PTV D 100.1 94.1 95.6 98.6 98.6 Mean 0.3 1.3 1.3 1.4 1.8 PTV D 94.1 95.5 98.5 98.5 5 Mean 1.3 1.1 1.3 1.8 PTV D 101.6 104.7 104.8 1.2 1.8 2.2 PTV D 103.1 103.2 5 95 1.6 2.0 ICRU RD (Case Mean) 100.0 1.3 IMRT PTV D 99.5 100.9 92.1 96.4 100.7 100.7 Median n = 10 0.3 0.3 2.2 1.0 1.1 2.8 PTV D 101.4 92.5 96.9 101.2 101.2 Mean 0.5 2.0 1.1 1.0 2.2 PTV D 91.3 95.6 99.9 99.9 5 Mean 2.3 1.1 1.0 2.7 PTV D 104.7 109.5 109.5 2.2 2.6 3.6 PTV D 104.5 104.5 5 95 1.7 3.1 ICRU RD (Case Mean) 100.0 2.5 without bolus CRT PTV D 98.8 100.6 88.0 96.4 99.3 99.3 Median n = 14 0.3 0.4 1.5 1.4 1.5 1.9 PTV D 101.8 89.0 97.5 100.5 100.4 Mean 0.3 1.3 1.3 1.4 1.8 PTV D 87.5 95.8 98.7 98.7 5 Mean 1.3 1.1 1.3 1.8 PTV D 109.7 113.0 112.7 1.2 1.8 2.2 PTV D 103.0 103.1 5 95 1.6 2.0 ICRU RD (Case Mean) 100.0 1.3 Page 7 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 3: Correlation of prescriptions (breast cases -- surface effects) (Continued) IMRT PTV D 97.7 101.4 81.5 96.3 102.1 102.1 Median n = 10 0.7 1.0 3.2 1.4 1.0 2.6 PTV D 103.8 83.5 98.6 104.6 104.6 Mean 1.4 2.9 1.9 1.5 2.9 PTV D 80.4 95.0 100.7 100.7 5 Mean 3.8 1.0 0.8 2.5 PTV D 118.3 125.5 125.5 6.4 6.1 6.6 PTV D 106.1 106.1 5 95 1.5 3.0 ICRU RD (Case Mean) 100.0 2.4 Correlation of several prescription and reporting methods. All methods report for the same dose distribution per study. -- Breast cases with and without bolus (upper and lower part, respectively). The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62 tion cannot be recommended in general. D is always more closely correlated to the ICRU RD, thereby making only weakly correlated to the ICRU RD for both, PTV and CRT and IMRT plans more comparable. particularly for PTV - in contrast to other methods (see Fig. 2b). Even compared with the single point - ICRU RD Moreover, for the breast cases (largest standard deviation Point correlation (with its standard deviation of 2% - relative to the ICRU RD; Table 3) and for some SIB in the 2.5% for IMRT plans) it is more loosely correlated with circumferential PTV (not shown in detail), the D pre- former ICRU RD. The conversion of a D prescription scription depends largely on surface effects (i.e. changes of would also be greatly affected by surface effects, as can be more than 5% for an irradiation with or without a bolus). seen for the CRT and IMRT breast cases (varying from 1.04 The exemplary DVH of a patient with three concentric to 1.25 in Table 3 and similar results for the outer SIB vol- head and neck target volumes in Fig. 1 depicts the same ume in Table 4). problem. Application of a 5 mm bolus changes the course of the PTV curve drastically at the low dose limb of the To compare IMRT results with earlier CRT results and to DVH. Obviously, minor changes in the placement of the assure continuity with respect to former dose prescription, bolus would influence a prescription based on D of the another substitute for ICRU RD must be provided. PTV PTV, although only the peripheral PTV areas are affected. D and PTV D (or D ...) may be reported as addi- Similarly, D depends clearly on further parameters. Cen- 95 min 01 95 tional information to describe the homogeneity of the tral volumes in our clinical practice tend to have much dose in the PTV. It should be noted that neither the dose lower D to ICRU RD ratios (1.040%, see Table 4) in con- below the D is restricted to the peripheral PTV areas nor trast to 107.0% and 106.9% for single or circumferential is the depth of a drastic dose reduction below the D PTVs. A prescription and reporting based on central areas restricted by using this prescription and reporting (CTV, PTV ) would be much more insensitive with respect method. Therefore, usage of D alone, can neither guar- to effects of surface and volume delineation variations. antee a certain lower limit for a tumour control probabil- ity nor "an expected clinical outcome of the treatment" This article is not intended to determine whether a [1]. Dose prescription and description of the plan quality D (PTV) or a D (PTV ) prescription would be the bet- 95 mean x cannot be achieved with a single parameter. An ASTRO/ ter method to prescribe tumour control. Both require AAPM working group recommends three DVH-points to more information about the low dose parts in relevant describe biologically relevant PTV-data of a dose distribu- areas that limit the tumour control probability (TCP) and tion [16]. Two of the points form the lower and upper hot spots that increase the probability of irreversible dam- dose limits, the third point should provide the dose "that age to healthy tissue. The D (PTV ) approach implies mean x covers the target" [16]. However, also mean and median additional information on the local behaviour of the dose doses in the PTV or PTV seem to be appropriate candi- distribution that is lost in the D concept: as can be seen x 95 dates to describe the "typical" dose, some of them much below, D (PTV ) together with additional information mean x Page 8 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 4: Correlation of prescriptions (non-breast IMRT subgroups - topological aspects) denominator\numerator PTV PTV PTV ICRU ICRU D D D RD RD Mean Mean 95 (Case-Mean) [%] [%] [%] [%] [%] Single PTV PTV D 99.5 100.7 94.1 100.6 100.6 Median n = 12 0.3 0.4 1.9 1.3 2.4 PTV D 101.2 94.6 101.1 101.1 Mean 0.6 1.8 1.4 2.5 PTV D 93.4 99.9 99.9 5 Mean 2.1 1.3 2.4 PTV D 107.0 107.0 2.8 3.5 Central PTV PTV D 100.0 101.0 96.5 100.4 100.4 Median n = 15 0.3 0.8 0.7 0.8 1.6 PTV D 100.9 96.5 100.4 100.4 Mean 0.8 0.8 0.9 1.6 PTV D 95.6 99.4 99.4 5 Mean 1.3 0.8 1.6 PTV D 104.0 104.0 1.4 2.0 Circumferential PTV PTV D 99.9 100.0 93.6 100.0 100.0 Median n = 20 1.3 1.2 2.4 2.2 3.4 PTV D 99.8 93.4 99.8 99.8 Mean 2.0 2.7 2.9 3.9 PTV D 93.8 99.7 99.7 5 Mean 2.4 1.6 2.9 PTV D 106.9 106.9 4.2 5.0 Correlation of several prescription and reporting methods for subgroups of IMRT plans (non-breast cases) without surface effects (with bolus and PTV-distance to patient outline > 5 mm). All methods report for the same dose distribution per study. The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62. Central and circumferential volumes together form the volumes of SIB (2 or 3 nested volumes) like the standard deviation of the dose distribution allows should be noted, that the standard deviations of the mean linkage to a more biologically based evaluation (see last doses in the PTV and the PTV (σ /D in Table 1) are x D mean section). comparable for single PTV IMRT and CRT plans. This means that the fluctuations of the dose in PTV or PTV as Dose fluctuations in the target a whole are comparable for CRT and this special type of The fluctuations of the ICRU RD increase for IMRT as pre- IMRT (IMRT based on the DMPO optimization). Con- dicted by several authors [7]: the standard deviation for versely, the standard deviations of the ICRU RD from sev- the ICRU RD is slightly larger for IMRT plans than for the eral chosen points tend to be smaller for CRT plans than CRT techniques, and all correlations of other methods are for IMRT plans ("PTV D " and "PTV D " in Table 2, mean 5 mean weaker for IMRT than for CRT (the standard deviation of 3 and 4, last column "ICRU RD"). Perhaps this can be the quotient of the reported results is larger). However, it interpreted as if dose fluctuations of classical CRT plans Page 9 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 cannot compensate a potential underdosage at the pla- teau. This effect depends clearly on the dose difference of inner and outer volumes and could be relevant for dose differ- ences of 10% and more; the overestimation of the plateau dose could exceed 3% if the CTV mean dose would be used. For PTV D an underdose to the peripheral areas and an mean overdose to the inner areas could compensate each other. But this effect depends on the geometry of each individual E tative evaluation) with t tially Figure 1 xample abutting the patient outline of a head and n heree ck IM adR jacent, nested targ T case (not used for qua ets, par- nti- case, as can be deduced from the higher standard devia- Example of a head and neck IMRT case (not used for tions of PTV D (Table 4, circumferential volumes), mean quantitative evaluation) with three adjacent, nested indicating overestimations and underestimations that targets, partially abutting the patient outline. DVH for compensate each other averaging PTV D over all irradiation with 6 MV photons and bolus (thickness 5 mm): mean patients. PTV avoids both problems. dashed line. Without bolus: solid line. Left diagram: Three x nested, adjacent, non-overlapping PTV. Right diagram: Three nested PTV (PTV shrunk by 5 mm). From left to right: Outer SIB with nested volumes with a thickness of less than or (circumferential) to inner (central) PTV. equal 2× form no dose plateau in the outer PTV (such vol- umes were not addressed within this work). These SIB cases cannot be described by a concept equivalent to ICRU were less concentrated in the areas that were typically cho- points, because no point can be found which would be sen for ICRU Reference Points. This underlines the representative for this volume. Such volumes are mostly requirement of a volume integrating prescription and described by their minimal dose or concepts like D , D 99 98 reporting method for IMRT, even for rather homogeneous etcetera. IMRT plan types as used in this work. Adding a bolus to a breast plan changes the PTV mean It should be noted that the homogeneity of IMRT plans dose with respect to the ICRU reference dose by 2%. This has continuously increased in the past few years. For head is due to surface effects that should actually not influence and neck as well as related cases an extensive exploration the prescription, which should be based on the dose of data from the first IMRT decade had been performed within the central dose plateau with the highest accumu- [3]. Published DVHs (between 1990 and 1998) for realis- lation of tumour cells. Furthermore, dose calculation tic cases including scatter and absorption σ was 3.3% up algorithms tend to create erroneous results at the patient to 11% of a target with more than 5 mm to the patient surface. Obviously a dose of 0% as can be seen in table 1 outline, the related mean value of comparable non-IMRT for CRT breast cases is absurd. This topic will not be rotational techniques was 3.1%, classical opposed fields addressed here in detail, but clearly such areas should be with electrons reached 6% which should be compared to omitted when important values as the prescription dose of the dose in PTV which are a mean of 2.2% for σ are to be determined. Similar changes of the PTV mean D 5 reached for DMPO in head and neck cases in this work. dose can be expected due to delineation effects of the PTV Sliding window or volumetric arc techniques should be shape [17,18]. The same observation can be made in the able to create even more homogeneous dose distribu- example from Fig. 1: mean values of the central plateau of tions. These results also encourage the use of "non-D " each target (PTV ) are not affected by using a bolus or not 95 5 plans, but prescription and reporting methods with a con- (right side), whereas manifestly the mean dose of the PTV version factor around 1.00 in relation to the hitherto valid itself significantly changes. ICRU RD, if CRT and IMRT plans should be compared. In non-SIB cases PTV could resemble CTV, which then SIB and surface effects of the PTV and CTV mean dose could be alternatively used for prescription and reporting. The mean dose to the CTV for the outer SIB volumes over- However, CTVs with points near the surface should be estimated the plateau dose by 2% (in some cases almost chosen with caution. As can be seen in the case of the tis- 4%). For these outer PTVs of SIB, the dose gradient sue of the mammary gland for slender patients, CTV towards the inner PTVs influences the mean dose of the sometimes approaches the outline more closely than 5 outer PTV. It raises the mean dose in the CTV, pretending mm. The choice of 5 mm is due to the fact that these 5 mm a higher dose as actually reached in the dose plateau, often are used in daily practice (i.e. Fogliata 2005) [13]. whereas the dose overkill near the inner gradient probably Page 10 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 $ $ $ % % % $ $ $ # # # " " " ! ! ! ! " # $ % $  ! " # $ % $  ! " # $ % $ centr Figure 2 Correlation of several prescrip ICRU 52/60 Reference Dose cr al part of the PTV) tion and repo iteria) with the ratio of th rting methods (all related to e prescriptions PTV ICRU RD, the D /ICRU RD (PTV mean value of 4 or 5 points fulfilling t D : mean dose for the he 5 mean 5 mean Correlation of several prescription and reporting methods (all related to ICRU RD, the mean value of 4 or 5 points fulfilling the ICRU 52/60 Reference Dose criteria) with the ratio of the prescriptions PTV D /ICRU 5 mean RD (PTV D : mean dose for the central part of the PTV). Results for all plans of the study. All methods report for 5 mean the same dose distribution per study. Circles: All IMRT plans and related volumes. Triangles: All CRT plans used in this study. left: PTV D vs. PTV D (dose to 95% of the PTV). middle: PTV D vs. PTV D . (median dose for the PTV) right: 5 mean 95 5 mean median PTV D vs. PTV D (mean dose of the PTV). 5 mean mean In summary, only median dose in the PTV and the mean This is not necessarily so for a D prescription - not even dose to the PTV remain in contention to be the worthy in the majority of cases. If a prescription point ought to be successor of the ICRU RD. Both were mutually strongly defined, it should be placed at the border of the PTV near correlated (standard deviation of the quotient of about to the steep dose gradients. (Only for IMRT plans with 1%) and could be converted using a factor of 1.00. dose gaps in the centre of the PTV- that is for bad plans - a reference dose point representing the prescription dose Additional advantages and disadvantages of the mean could be placed somewhere in the central PTV area.) dose in PTV The definition of PTV includes the set of all points which In contrast to the prescription and reporting based on the can be chosen as ICRU Reference Points as a subset. Per- median dose which is regarded as a relevant method, the haps, PTV could even be interpreted as the set of all mean value of PTV could be a base for later biological x x points that could possibly be chosen as ICRU Reference interpretations with diverse biological models [5,14]. Points. Therefore, the close correlation to the special Brahme demonstrated that the pair of mean value and choice of ICRU Reference Points in this work is not sur- standard deviation σ of the dose in a volume with con- prising. The x = 5 mm margin ensures that all points are stant tumour cell density provides the possibility of the within a dose plateau and not near to the steep dose gra- subsequent approximate recalculation of tumour control dient at the borders of the PTV. In several cases, PTV probabilities or equivalent doses with arbitrary biological includes about 58% (32% to 73%) of the PTV volume for models [19]. (PTV is a better approximation of such a vol- the CRT and 41% (7% to 77%) for the IMRT cases. Fur- ume than PTV with its much smaller tumour cell densities thermore, all the excluded voxels are supposed to have a in the periphery.) Bleher et al. calculated a σ correction lower tumour cell density than the centre of the PTV, of the tumour control probability for a known "homoge- which includes the CTV. Due to the mean value theorem neous dose" probability curve TCP(D) [20]: for integration, the mean value of PTV can be represented by one or more points within the plateau PTV of the PTV. 2 (1a) TCP(D )=⋅ TCP() D exp(−k() D⋅s ) eff D Page 11 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 The first non-trivial non-zero term of a Taylor-series Conclusion around D = D (PTV ) with "The dose to the patient", formerly represented by the mean x ICRU Reference Point, continues to play a prominent role in daily practice (i.e. the doctor's letter). In contrast the ⎡ 2 ⎤ TCP ’(D)−⋅ TCP(D) TCP ’’(D) intended additional values in ICRU 62 [2], the expanded kD () = ⎢ ⎥ . (1b) ⎢ ⎥ TCP() D framework of these recommendations, sometimes tend to ⎣ ⎦ be in the background - all the more reason that a careful and coherent definition of this dose term is performed. The definition of PTV additionally allows the evaluation of D of the dose in the central PTV area - PTV - and the min x As successor for the ICRU Reference Point, equally usable standard deviation σ of the dose therein. Both are useful for IMRT and CRT, the authors recommend the median to control the dose homogeneity in the most important dose to the PTV or - preferably - the mean dose to the part of the PTV. For the whole PTV, potential dose inho- PTV , the central plateau. Both are "near" to the physical mogeneities in the centre are covered by the dominating dose distribution and provide a consistent extension of dose inhomogeneities at the periphery, which is caused by the ICRU Reference Dose (strong correlation and conver- uncertainties of the PTV definition or uncertainties in the sion factor ≈ 1.00). Mean doses to CTV and PTV do not to dose calculation (dose grid, surface effects). Therefore, such an extent. Usage of PTV D adds the possibility of D and σ of the PTV are less meaningful than D and x mean min D min using of the standard deviation in the PTV for later evalu- σ of the CTV or PTV . Such information - PTV D and D x x min ation of tumour control probabilities. Moreover it pro- σ - is routinely used in our clinic for automatic control of vides further parameters, which control the homogeneity these aspects of plan quality. In our institution, σ < 3.3% of the target (like standard deviation and minimal dose to is striven for to avoid relevant TCP-reductions due to the central plateau). inhomogeneity. For γ = 3 (the steepness of TCP-curve) and σ < 3.5% Brahme estimated a decrease of 5% for the TCP. Competing interests The authors declare that they have no competing interests. An additional advantage of the mean dose in the PTV is the additivity of mean doses in contrast to median doses Authors' contributions or D , albeit the biologically equivalent doses cannot KB was responsible for the primary concept and the simply be summed up. design of the study; he compiled the results and drafted the manuscript; MO evaluated most of the results; MG Some limitations of the D (PTV ) concept should not mean x critically accompanied the study and revised the manu- be concealed. For example for stereotactic treatments, script; MF was responsible for the patients, reviewed dose inhomogeneity may be intended. This inhomogene- patient data and revised the manuscript. All authors read ity is not arbitrary. The hot spots for small volumes are and approved the final manuscript. preferably in the central CTV. Commonly minimal doses (D with small y) in the CTV and PTV together with 100-y Acknowledgements maximum doses (D with small z) are reported. All these This work was in part supported by the German Research Foundation prescription values are relevant. Nevertheless even in the (Deutsche Forschungsgemeinschaft - DFG Project Code DFG BR 3460/2). case of stereotactic irradiations, a wider plateau with steep gradient near the PTV edge and a sharply peaked dose dis- This work was in part used for oral presentation at the 11th World Con- tribution with less steep gradient could be delivered with gress on Medical Physics and Biomedical Engineering, Munich 2009. the same specific data as stated above, although the former dose distribution would obviously provide the References better TCP. The additional use of D (PTV ) would 1. ICRU: Prescribing, recording, and reporting photon beam mean x therapy. In ICRU report Volume 50. Bethesda: International Commis- reveal the differences of both plans. sion on Radiation Units and Measurements; 1993. 2. ICRU: Prescribing, recording, and reporting photon beam As a further disadvantage it should be noted that PTV is therapy (supplement to ICRU report 50). In ICRU Report Vol- ume 62. Bethesda: International Commission on Radiation Units and currently not in usage (as long as it is not chosen identical Measurements; 1999. with the CTV). Additionally the choice of x (x = 5 mm in 3. Bratengeier K, Pfreundner L, Flentje M: Radiation techniques for head and neck tumors. Radiotherapy and Oncology 2000, this work) is arbitrary. 56:209-220. 4. Kukolowicz PF, Mijnheer BJ: Comparison between dose values If the usage of PTV is considered to be too arbitrary, a specified at the ICRU reference point and the mean dose to the planning target volume. Radiother Oncol 1997, 42:271-277. "modified CTV" could be used as a compromise: A CTV 5. Das IJ, Cheng CW, Chopra KL, Mitra RK, Srivastava SP, Glatstein E: reduced by margins to other CTVs in the vicinity. Intensity-modulated radiation therapy dose prescription, recording, and delivery: patterns of variability among institu- Page 12 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 tions and treatment planning systems. J Natl Cancer Inst 2008, 100:300-307. 6. Willins J, Kachnic L: Clinically relevant standards for intensity- modulated radiation therapy dose prescription. J Natl Cancer Inst 2008, 100:288-290. 7. Yaparpalvi R, Hong L, Mah D, Shen J, Mutyala S, Spierer M, Garg M, Guha C, Kalnicki S: ICRU reference dose in an era of intensity- modulated radiation therapy clinical trials: correlation with planning target volume mean dose and suitability for inten- sity-modulated radiation therapy dose prescription. Radiother Oncol 2008, 89:347-352. 8. Purdy JA: Intensity-modulated radiotherapy: current status and issues of interest. Int J Radiat Oncol Biol Phys 2001, 51:880-914. 9. Holmes T, Das R, Low D, Yin FF, Balter J, Palta J, Eifel P: American Society of Radiation Oncology recommendations for docu- menting intensity-modulated radiation therapy treatments. Int J Radiat Oncol Biol Phys 2009, 74:1311-1318. 10. Mohan R, Wu Q, Manning M, Schmidt-Ullrich R: Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck can- cers. Int J Radiat Oncol Biol Phys 2000, 46:619-630. 11. Earl MA, Shepard DM, Naqvi S, Li XA, Yu CX: Inverse planning for intensity-modulated arc therapy using direct aperture opti- mization. Phys Med Biol 2003, 48:1075-1089. 12. Bratengeier K, Meyer J, Flentje M: Pre-segmented 2-Step IMRT with subsequent direct machine parameter optimisation - a planning study. Radiat Oncol 2008, 3:38. 13. Fogliata A, Nicolini G, Alber M, Asell M, Dobler B, El-Haddad M, Har- demark B, Jelen U, Kania A, Larsson M, Lohr F, Munger T, Negri E, Rodrigues C, Cozzi L: IMRT for breast. a planning study. Radi- other Oncol 2005, 76:300-310. 14. Grégoire V, Mackie TR: ICRU committee on volume and dose specification for prescribing, recording and reporting special techniques in external photon beam therapy: conformal and IMRT. Radiotherapy and Oncology 2005, 76:S71. 15. Wambersie A, DeLuca P, Gahbauer R, Whitmore G: Recent devel- opments of the ICRU Program in Radiation Therapy: "Pre- scribing, Recording and Reporting Modern Treatment Modalities: IMRT, Cervix Brachytherapy, Proton- and Ion- Beam Treatment. Radiotherapy and Oncology 2006, 81:S117-S118. 16. Galvin JM, Ezzell G, Eisbrauch A, Yu C, Butler B, Xiao Y, Rosen I, Rosenman J, Sharpe M, Xing L, Xia P, Lomax T, Low DA, Palta J: Implementing IMRT in clinical practice: a joint document of the American Society for Therapeutic Radiology and Oncol- ogy and the American Association of Physicists in Medicine. Int J Radiat Oncol Biol Phys 2004, 58:1616-1634. 17. Ketting CH, Austin-Seymour M, Kalet I, Unger J, Hummel S, Jacky J: Consistency of three-dimensional planning target volumes across physicians and institutions. Int J Radiat Oncol Biol Phys 1997, 37:445-453. 18. Lawton CA, Michalski J, El-Naqa I, Kuban D, Lee WR, Rosenthal SA, Zietman A, Sandler H, Shipley W, Ritter M, Valicenti R, Catton C, Roach M 3rd, Pisansky TM, Seider M: Variation in the Definition of Clinical Target Volumes for Pelvic Nodal Conformal Radi- ation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys 2008, 72:377-382. 19. Brahme A: Dosimetric precision requirements in radiation therapy. Acta Radiol Oncol 1984, 23:379-391. 20. Bleher M, Bratengeier K, Richter J: Assessment of radiotherapy plans: dose-volume histograms, integral effects and tumor control. Strahlenther Onkol 1991, 167:220-226. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 13 of 13 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Remarks on reporting and recording consistent with the ICRU Reference Dose

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Springer Journals
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Copyright © 2009 by Bratengeier et al; licensee BioMed Central Ltd.
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Medicine & Public Health; Oncology; Radiotherapy
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1748-717X
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10.1186/1748-717X-4-44
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19828045
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Abstract

Background: ICRU 50/62 provides a framework to facilitate the reporting of external beam radiotherapy treatments from different institutions. A predominant role is played by points that represent "the PTV dose". However, for new techniques like Intensity Modulated Radiotherapy (IMRT) - especially step and shoot IMRT - it is difficult to define a point whose dose can be called "characteristic" of the PTV dose distribution. Therefore different volume based methods of reporting of the prescribed dose are in use worldwide. Several of them were compared regarding their usability for IMRT and compatibility with the ICRU Reference Point dose for conformal radiotherapy (CRT) in this study. Methods: The dose distributions of 45 arbitrarily chosen volumes treated by CRT plans and 57 volumes treated by IMRT plans were used for comparison. Some of the IMRT methods distinguish the planning target volume (PTV) and its central part PTV (PTV minus a margin region of × mm). The reporting of dose prescriptions based on mean and median doses together with the dose to 95% of the considered volume (D ) were compared with each other and in respect of a prescription report with the aid of one or several possible ICRU Reference Points. The correlation between all methods was determined using the standard deviation of the ratio of all possible pairs of prescription reports. In addition the effects of boluses and the characteristics of simultaneous integrated boosts (SIB) were examined. Results: Two types of methods result in a high degree of consistency with the hitherto valid ICRU dose reporting concept: the median dose of the PTV and the mean dose to the central part of the PTV (PTV ). The latter is similar to the CTV, if no nested PTVs are used and no patient model surfaces are involved. A reporting of dose prescription using the CTV mean dose tends to overestimate the plateau doses of the lower dose plateaus of SIB plans. PTV provides the possibility to approach biological effects using the standard deviation of the dose within this volume. Conclusion: The authors advocate reporting the PTV median dose or preferably the mean dose of the central dose plateau PTV as a potential replacement or successor of the ICRU Reference Dose - both usable for CRT and IMRT. Page 1 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 IMRT-plans. Additionally, simultaneous integrated boost Background ICRU 50 and ICRU 62 provide a framework which struc- (SIB) IMRT cases were considered, in which nested dose tures the reporting of external beam radiotherapy treat- plateaus are formed [10]. To describe the dose to a plateau ments from different institutions [1,2]. These reports refer and to exclude effects of a dose gradient at the border of to conventional conformal radiation techniques (CRT). each volume, the authors preferred to define volumes that Within that framework, the definition of points that rep- are distant to each other. This condition cannot be ful- resent "the PTV dose", "prescription dose" or "intended filled by the clinical target volume (CTV) in the cases of dose" plays a predominant role. SIB. Since then, new techniques like Intensity modulated radi- Methods otherapy (IMRT) have been introduced. Early IMRT could In this retrospective study, treatment planning was per- only create more inhomogeneous dose distributions, as it formed on a Philips Pinnacle3™ version 8.0 m planning was shown by Bratengeier et al. for head and neck studies system (Philips Radiation Oncology Systems, Fitchburg, [3]. Even if today IMRT can be planned more homogene- Wi, USA). Siemens Primus™ (Siemens Healthcare, Erlan- ously, the positioning of a point whose dose can be called gen, Germany) and Elekta Synergy™ (with BeamModula- "characteristic" of the planning target volume (PTV) is tor™; Elekta AB, Stockholm, Sweden) linacs were regarded as difficult, if not ambiguous. Therefore the def- commissioned with 10 mm or 4 mm leaf width (in the inition of the ICRU Reference Point has become problem- isocentre), respectively. The CT slice distance was 3 or 5 atic. Previous work like that of Kukolowicz et al. has to be mm. A dose grid size of between 2 and 4 mm was chosen. revised for application to IMRT [4]. As a result of the loss The step and shoot IMRT plans are optimised by the Ray- of significance of the ICRU Reference Point, a plurality of search™ direct machine parameter optimisation (DMPO) volume based dose concepts are currently contending, module, a direct aperture optimisation (DAO) method such as the mean dose to the PTV (PTV D ) and the [11]. Not more than 50 segments per plan were used. mean clinical target volume CTV (CTV D ), the dose to 95% IMRT plans were irradiated with 7, or (mostly) 9 equidis- mean of the PTV (PTV D ) and others [5-7]. The IMRT Collab- tant beams or 10 non-equidistant fields (breast cases) orative Working Group recommended the reporting of [12]. The dose distribution was calculated using a col- "Prescribed (intended) dose, as well as the point or vol- lapsed cone algorithm. ume to which it is prescribed; ....Dose that covers 95% (D95) of the PTV and CTV. Dose that covers 100% The patient data were randomly selected from the normal (D100) of the PTV and CTV (i.e., the minimal dose). clinical routine. 70 patients with different tumour locali- Mean and maximal doses within the PTV and CTV. Per- sations and a total of 102 treatment plans were examined. centage of the PTV and CTV that received the prescribed 12 plans resulted from technique changes; 24 plan vari- dose (V100)...." [8]. A recent ASTRO recommendation ants resulted from the application or removal of a bolus. added some further details to be recorded - i.e. D , D , For CRT 38 patients with several localizations were cho- mean 0 D , D , V in PTV and CTV additional to the "pre- sen (i.e. 10 head and neck cases, 9 tumours of the abdo- 95 100 100 scribed dose" [9]. men, 7 breast patients with 2 plan each, 4 metastases). 37 patient models with 57 target volumes were used for IMRT Often the PTV D is used as prescribed dose because it is techniques (i.e. 19 head and neck patients, 10 breast supposed to be a dose prescription regarding biological patients). 6 MV photons were applied for breast, head and aspects [7]. This is popular in studies of the Radiation neck tumours, 10 MV or 18 MV for the tumours of the ® ® Therapy Oncology Group (RTOG ), i.e. the protocols abdomen. 0022, 0522, 0615, 0619. This procedure differs from the Volume definitions and methods of dose prescription and ICRU Reference Dose concept and the correlation of these two concepts is unclear. reporting All volumes came from clinical practice and were ran- For that reason, the authors examined different volume domly selected. Only one planning target volume was based definitions. In particular, their consistency with the changed for the sake of this study. In addition to the clin- currently valid "ICRU Reference Dose" (ICRU RD, the ical target volume (CTV) and the planning target volume dose at the ICRU Reference Point) is investigated. In par- PTV we defined a "PTV " in which the volume is shrunk by ticular the ratio of the dose defined by several possible an amount × mm, and maintains a distance of × mm ICRU Reference Points and the dose defined by the differ- towards air. It should be noted that for SIB the nested ent reporting procedures is investigated for the same plan. PTVs abut each other. PTV then excludes the high dose Moreover, the correlation of the pairwise application is area just as the low dose areas of the PTV. This volume is explored by calculating the standard deviation of these designated as the "central target volume". It is used to ratios for all plans and target volumes. Definitions are describe the plateau dose. It comprises, depending on the applied to classical (forward planning) CRT plans and to choice of x, approximately the clinical target volume Page 2 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 (CTV) in the non-SIB cases. Contrary to the CTV it is large lung areas, or if the volumes included mammaria designed to contain all the points that eventually would interna lymph nodes. The mean volume for IMRT breast be allowed to be chosen as ICRU dose prescription points; cases was therefore larger than for CRT. the points from the CTV or PTV from the dose gradient area towards an inner PTV would not comply with that In this study the arithmetic mean and median averages of condition. PTV shells that are generated using a margin of the dose distribution in the PTV and PTV were evaluated. less than 2× around an inner target volume would not In addition D in PTV and PTV were determined. Their 95 5 form a dose plateau and PTV is not defined for the outer relationships were calculated for a plurality of ICRU Ref- PTV ring. This situation will be addressed in the discus- erence Points selected according to ICRU criteria. For the sion section. For this planning study x = 5 mm was conventional plans 236 points were used which were selected, a distance that is frequently chosen to avoid sur- acceptable ICRU reference points, for the IMRT plans 340 face effects [13]. In all conventional cases and 22 IMRT- points. The ICRU Reference Point criteria are: "(1) the cases only one PTV exists. In 15 IMRT-cases 35 nested tar- dose to the point should be clinically relevant; (2) the get volumes were selected and simultaneously irradiated point should be easy to define in a clear and unambigu- (SIB) [10]. The target volumes are fundamentally non- ous way; (3) the point should be selected so that the dose overlapping. Therefore, for SIB they abut one another. The can be accurately determined; (4) the point should be in extension of the volumes is presented in Table 1. a region where there is no steep dose gradient." [2]. The commission added: "These recommendations will be ful- For breast cases, IMRT was only used to replace CRT if the filled if the ICRU reference point is located: - always at the PTV was extremely curved and standard fields included centre (or in a central part) of the PTV,..." Table 1: Overview Non-breast Breast with bolus Breast without bolus CRT IMRT CRT IMRT CRT IMRT Single PTV SIB SIB Central Circumferential PTV PTV n31 47 12 15 20 14 10 14 10 Vol [cm]PTV 837 430 918 124 367 1240 1576 1240 1576 546 471 671 76 212 467 1100 467 1100 PTV 512 202 522 42 127 797 1042 797 1042 383 311 471 37 96 349 823 349 823 σ /D PTV 4.4 3.9 4.0 2.2 5.0 3.9 4.5 7.0 9.0 D mean [%] 2.0 1.8 1.5 0.7 1.7 0.9 1.1 0.9 1.3 PTV 2.3 2.1 2.1 1.6 2.5 2.9 2.8 2.7 3.1 0.7 0.7 0.7 0.6 0.6 0.6 0.7 0.6 0.7 D /D PTV 48.4 51.2 31.1 81.9 40.2 23.7 41.4 0 2.5 min mean [%] 33.7 35.0 37.3 16.7 28.7 24.0 21.7 0 4.2 PTV 85.8 88.3 85.2 95.4 84.7 92.0 85.7 86.6 81.0 10.7 17.6 21.6 1.7 20.6 2.3 7.6 2.3 4.9 D /D PTV 109.6 111.9 109.4 106.9 117.0 111.7 114.3 112.3 116.7 max mean [%] 4.5 6.8 3.2 2.6 7.0 3.0 3.3 3.0 3.0 PTV 108.3 108.4 107.4 104.9 111.8 110.3 112.4 109.6 112.4 4.3 4.5 2.7 2.1 4.5 2.6 3.5 2.6 3.4 n: Number of volumes with related plans. Mean values of Volumes (Vol). Standard deviations of the dose distributions σ , dose minima and maxima (D , D ), divided by the mean doses (D ) within PTVs and PTV shrunk by 5 mm (PTV ) for several groups of plans (CRT: Conformal min max mean 5 radiotherapy, IMRT: Intensity modulated radiotherapy; SIB: Simultaneous Integrated Boost). The upper value in each cell is the mean value; the lower value is the corresponding standard deviation Page 3 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 In almost all cases, four such points are positioned in the the surface on the PTV standard deviation can clearly be central part of each target volume. If possible, one of these seen, whereas the standard deviation of PTV is not points was placed in the centre in the central plane of the affected. For IMRT, the relative standard deviation of the PTV. For IMRT plans with single PTVs, additionally the dose in the PTV (PTV ) was 3.9% (2.1%) for the non- isocentre was chosen as fifth point. The other points were breast plans, 9.0% (3.1%) for the breast plans without arbitrarily placed in areas which seemed homogeneous. bolus and 4.5% (2.8%) for the same plans with bolus The minimum distance between the points was 1 cm, 0.5 (Table 1). This result is similar to that for the CRT-plans, cm for SIB PTVs. The dose to the isocentre and the mean indicating that for step and shoot IMRT using DMPO sim- dose of the other four possible ICRU Reference Points ilar dose homogeneity could be achieved as for the CRT were compared. plans, although the PTV shape was more complex. A detailed view of the IMRT results shows differences for the Furthermore the standard deviations of the doses in the inner PTV (σ = 2.2% (1.6%)) and the annular PTV shells PTV and PTV were determined. Keeping in mind that D (σ = 5.0% (2.5%)). For the latter, the standard deviation 5 0 D (= maximum dose) and D (= minimum dose) can be and hence dose homogeneity suffers especially in the PTV defective, these values are provided as additional informa- from the additional dose gradient towards the inner target tion. volumes. These findings were similar, if CTV was used instead of PTV for nested volumes: the standard deviation Subgroups of patients are created to allow a cross-check of increased by a factor of 1.5, (for 3 of 26 volumes by more the data. than a factor of 2; details see below). Effects of SIB and surface effects The minimum doses for CRT were around 31% (86%) in The characteristics of the 15 head and neck SIB plans were relation to the prescription dose, for IMRT 44% (86%) evaluated. These cases were sorted according to their with large standard deviations of 33% (10%) and 34% topology: The central PTV and the (one or two) circumfer- (16%), respectively. (not shown in the tables). However, ential PTVs. these results can largely be influenced by PTV delineation, surface effects, grid size and dose calculation algorithm. Surface effects at the patient model surface can drastically change even for a slight change of the outline. The behav- The isocentres in the single PTV IMRT cases were used to iour of the different prescription and reporting methods control the adequate setting of the arbitrary chosen ICRU in such situations was investigated by quantifying the reference points. The mean value of their doses differed by effect of the removal of the bolus for configurations which a factor of 0.9995 and the standard deviations were 2.2% were initially planned and optimized with bolus. In clini- and 2.4%, respectively. This indicates a reasonable ICRU cal practice, a bolus can be removed or added according to Reference Point positioning in this work. the skin reaction. The prescription must not change in an Comparison of prescription and reporting methods other way as the dose to the central points in the PTV (just as for ICRU Reference Points). The breast patients were Table 2 correlates some volume based prescription and especially evaluated: Their PTV is near to the patient out- reporting methods and a selection of allowed ICRU Refer- line. Thus they are particularly suited to examine surface ence Points with an ICRU Reference Dose (RD) for non- effects. On the one hand the dose prescription reporting breast plans. The first row of each cell is the ratio of the using the PTV and the PTV were compared. On the other method of a column and to that of a row, averaged over hand the influence of using a bolus of 5 mm thickness all cases. In the second row the respective standard devia- covering the whole breast was tested both for CRT and tion of this average process is presented which indicates IMRT. The bolus was generated by the planning system the dispersion of the data. Ratios of the reported dose for not considering loose contact to the skin as often can be an identical dose distribution can be compared using the observed in clinical practice. Hence, in the breast group upper and the lower part of the table for CRT and IMRT, two extremes are compared, because in clinical practice respectively. ICRU RD (case-mean) is the dose to the neither such a perfect bolus is available nor would the mean value of all chosen examples of an ICRU Reference cases with skin involvement be irradiated without a bolus. Point of each case, finally averaged over all cases. In the right column, ICRU RD, the average of all normalized Results ICRU Dose Points of all cases is presented to show the sta- Plan quality parameters tistical dispersion if different single points are used to rep- The relative standard deviation of the doses in the PTV resent a dose distribution. (PTV , respectively) was 4.4% (2.3%) for the CRT non- breast plans, 7.0% (2.7%) for the breast plans without The standard deviation of the ratio ICRU RD/ICRU RD bolus and 3.9% (2.9%) for the same plans with a bolus (case-mean) - last row, right column - is a measure of the over the whole breast (see also Table 1). The influence of statistical dispersion of the dose at the chosen ICRU Ref- Page 4 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 2: Correlation of prescriptions (non-breast cases) denominator\numerator PTV PTV PTV PTV ICRU ICRU 5 5 D D D D RD RD Mean Mean 95 95 (Case-Mean) [%] [%] [%] [%] [%] [%] CRT PTV D 99.5 100.4 92.4 96.6 99.9 99.9 Median n = 35 0.4 0.6 2.9 1.0 1.4 1.8 PTV D 100.9 92.8 97.1 100.5 100.5 Mean 0.7 2.9 1.2 1.7 2.0 PTV D 92.0 96.2 99.5 99.5 5 Mean 3.1 1.0 1.5 1.8 PTV D 104.7 108.3 108.0 3.1 4.0 4.2 PTV D 103.5 103.4 5 95 1.8 2.1 ICRU RD (Case Mean) 100.0 1.1 IMRT PTV D 100.0 100.5 94.7 97.2 100.3 100.3 Median n = 47 0.8 1.0 2.3 1.5 1.7 2.7 PTV D 100.5 94.7 97.3 100.3 100.4 Mean 1.5 2.4 1.9 2.1 3.0 PTV D 94.3 96.8 99.7 99.7 5 Mean 2.2 1.1 1.3 2.4 PTV D 102.6 107.0 107.0 2.0 2.8 3.5 PTV D 103.0 103.0 5 95 1.8 2.7 ICRU RD (Case Mean) 100.0 2.1 Correlation of several prescription and reporting methods. All methods report for the same dose distribution per study. -- Non-breast cases. The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62 erence Points within a volume, a measure of the correla- ICRU Reference Point was biased by less than 0.6% (when tion among the chosen points. This value should be using all CRT and IMRT plans), whereas the quotient for improved upon by any method which competes with the PTV D was 96% and for PTV D 92%. The D values 5 95 95 95 point based methods. Standard deviations of 1.3% and should be compared with an independent evaluation in 2.3% for the ICRU RD point to point correlations are the author's clinic over 350 patients: there a value of found for all CRT plans and all IMRT plans, respectively 94.3% for a mixture of both PTV groups was achieved. (not shown in the tables). They should also be considered as benchmarks for the correlation of the ICRU RD with A cross-check of dose reporting concepts for the breast any other reporting method: the standard deviations over cases (with bolus; Table 3) and for non-breast, single PTV all plans were 1.5% and 1.4% for PTV D , 1.6% and IMRT (Table 4) reveals almost the same results. Only the 5 mean 1.8% for PTV D , 1.9% and 2.6% for PTV D , 1.7% dose was slightly more homogeneous for single PTV IMRT median mean and 2.2% for PTV D , 4.3% and 5.9% for PTV D (CRT (Table 1). Consequently, the correlation of one ICRU Ref- 5 95 95 and IMRT, respectively). For the first three reporting meth- erence Point with the mean value of all possible ICRU Ref- ods, the average quotient with the reporting using the erence Points expressed by the standard deviation was Page 5 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 2.0% for non breast IMRT in a single PTV (not shown in with patient group characteristics similar to the non- the tables) compared with 2.6% for breast IMRT (Table 3). breast patient group of this work. The prescription dose , D , D and the dose had been correlated with D min max median For non-breast plans the reporting using PTV D , PTV to the isocentre. Except the median dose all parameters median D and PTV D led to comparable results with showed only weak correlation to the prescription dose. mean 5 mean respect to the mean of the ICRU Reference Doses. The These results agree with the results of this work. In Das' larger standard deviations for the ICRU RD reflect the fluc- work, the standard deviation of the ratio of prescription tuation due to the choice of the position of the ICRU Ref- dose and median dose as a measure of the correlation can erence Point. The results for CRT and IMRT are quite be estimated to be between 2% and 3%. In this work, the similar. standard deviation of the ratio ICRU RD (single point) and D was 1.8% for CRT and 2.7% for IMRT plans of median D was not presented in the tables because the standard the non-breast cases (Table 2). The latter value was mainly min deviation of the correlation to other methods was always influenced by SIB cases with onion-skin-like (nested) above 10% for D of PTV and even exceeded 30% for PTVs (3.4%). Otherwise the standard deviation was 2.4% min 5 of PTV. D (single PTV) and 1.6% (central PTV in a SIB constellation min - see Table 4). Thus, the results are similar. Detailed data for subgroups of non-breast IMRT are shown in Table 4. Here 12 patients with a single PTV are Yaparpalvi et al. examined the IMRT plans of 117 patients, differentiated from patients with SIB. For the latter, the 15 some of them with 3 different IMRT plans [7]. They com- central volumes and the 20 circumferential volumes were pared three prescription and reporting methods: the site distinguished. Only volumes with distances of at least 5 specific RTOG guideline, ICRU RD and D . Their mean mm to the patient model outline or plans with boluses results showed a strong correlation of D and ICRU RD mean were considered. with an estimated σ of roughly 2% (from Yaparpalvi Fig. 1) and a much weaker correlation of both with the D , For SIB IMRT, the dose ratio (PTV mean dose) of the D , D -prescriptions of several RTOG protocols. The 5 97 98 outer to the adjacent inner volume was 0.89 (0.82 up to ratio of prescription dose due to the RTOG guidelines and ) and 0.93) for the cases with 2 volumes, 0.87 (0.78 up to 0.92) the ICRU RD was between 103.6% (RTOG 0418, D for cases with 3 nested volumes (outer volume pair) and 105.1% (RTOG 0022, D ); the latter should be compared 0.96 (0.94 ... 0.99) (inner volume pair). Comparing the with the non-breast cases of this work (107.0% for all standard deviations of PTV and CTV for the related outer non-breast IMRT cases; 107.0% and 106.9% for single volumes, the standard deviation of the dose distributions and circumferential volumes, 104.0% for the central vol- increased for the CTV by a factor of 1.49, 1.86 and 1.08, ume of a SIB). They also concluded that the D in the median respectively. The mean dose to the CTV increased with PTV would be a better representation of the ICRU RD than respect of the mean dose to the PTV was by a factor of the D agrees with the results of this work. 5 mean 1.018, 1.019 and 1.005, respectively. Selecting the volume pairs with PTV mean dose differences of more than 9% Several meeting contributions have addressed future (10% up to 22%) between inner and outer PTV, led to ICRU recommendations on dose prescription, recording CTV/PTV dose ratios of 1.029; the ratio of the CTV/PTV and reporting [14,15]: Single point prescription and 5 5 standard deviations was 2.11 (1.68 to 2.89), respectively. reporting will be given up in favour of volume based methods. It was announced that the median dose would Table 3 presents the planning results of the breast cases play a prominent role. This is supported by this work, (CRT: 14 cases; IMRT: 10 cases). The upper part comprises although PTV could be a concept of more biological rele- the cases with 5 mm boluses, whereas the lower part rep- vance, in combination with the related standard deviation resents the same cases without a bolus. This table demon- in this volume (see below). strates the effect of the extended near-surface areas as typical for breast patients (the PTV is delineated approach- The use of PTV D ing the patient outline). Similar results were achieved if The use of D as a substitute or successor for the ICRU RD the bolus for five non-breast cases was removed (not would lead to a conversion factor of typical 1.08 ± 0.04 shown here, see Fig. 1). between PTV D and ICRU RD (non-breast plans, Table 2). Such a factor ought to be considered, if the prescrip- Discussion tion specification is changed. i.e. using PTV D instead of Comparison with other published results PTV D without adequate correction of the prescribed mean Das et al. compared the IMRT practice of five institutions dose would lead to a dose escalation. However, because of with differing planning systems [5]. 803 brain, head and the weakness of the correlation - expressed by the stand- neck and prostate cancer patient plans were evaluated, ard deviation of 2.8 to 4% (see Fig. 2) - such a transforma- Page 6 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 3: Correlation of prescriptions (breast cases -- surface effects) denominator\numerator PTV PTV PTV PTV ICRU ICRU 5 5 D D D D RD RD Mean Mean 95 95 (Case Mean) [%] [%] [%] [%] [%] [%] with bolus CRT PTV D 99.9 100.0 94.1 95.5 98.5 98.5 Median n = 14 0.3 0.4 1.5 1.4 1.5 1.9 PTV D 100.1 94.1 95.6 98.6 98.6 Mean 0.3 1.3 1.3 1.4 1.8 PTV D 94.1 95.5 98.5 98.5 5 Mean 1.3 1.1 1.3 1.8 PTV D 101.6 104.7 104.8 1.2 1.8 2.2 PTV D 103.1 103.2 5 95 1.6 2.0 ICRU RD (Case Mean) 100.0 1.3 IMRT PTV D 99.5 100.9 92.1 96.4 100.7 100.7 Median n = 10 0.3 0.3 2.2 1.0 1.1 2.8 PTV D 101.4 92.5 96.9 101.2 101.2 Mean 0.5 2.0 1.1 1.0 2.2 PTV D 91.3 95.6 99.9 99.9 5 Mean 2.3 1.1 1.0 2.7 PTV D 104.7 109.5 109.5 2.2 2.6 3.6 PTV D 104.5 104.5 5 95 1.7 3.1 ICRU RD (Case Mean) 100.0 2.5 without bolus CRT PTV D 98.8 100.6 88.0 96.4 99.3 99.3 Median n = 14 0.3 0.4 1.5 1.4 1.5 1.9 PTV D 101.8 89.0 97.5 100.5 100.4 Mean 0.3 1.3 1.3 1.4 1.8 PTV D 87.5 95.8 98.7 98.7 5 Mean 1.3 1.1 1.3 1.8 PTV D 109.7 113.0 112.7 1.2 1.8 2.2 PTV D 103.0 103.1 5 95 1.6 2.0 ICRU RD (Case Mean) 100.0 1.3 Page 7 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 3: Correlation of prescriptions (breast cases -- surface effects) (Continued) IMRT PTV D 97.7 101.4 81.5 96.3 102.1 102.1 Median n = 10 0.7 1.0 3.2 1.4 1.0 2.6 PTV D 103.8 83.5 98.6 104.6 104.6 Mean 1.4 2.9 1.9 1.5 2.9 PTV D 80.4 95.0 100.7 100.7 5 Mean 3.8 1.0 0.8 2.5 PTV D 118.3 125.5 125.5 6.4 6.1 6.6 PTV D 106.1 106.1 5 95 1.5 3.0 ICRU RD (Case Mean) 100.0 2.4 Correlation of several prescription and reporting methods. All methods report for the same dose distribution per study. -- Breast cases with and without bolus (upper and lower part, respectively). The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62 tion cannot be recommended in general. D is always more closely correlated to the ICRU RD, thereby making only weakly correlated to the ICRU RD for both, PTV and CRT and IMRT plans more comparable. particularly for PTV - in contrast to other methods (see Fig. 2b). Even compared with the single point - ICRU RD Moreover, for the breast cases (largest standard deviation Point correlation (with its standard deviation of 2% - relative to the ICRU RD; Table 3) and for some SIB in the 2.5% for IMRT plans) it is more loosely correlated with circumferential PTV (not shown in detail), the D pre- former ICRU RD. The conversion of a D prescription scription depends largely on surface effects (i.e. changes of would also be greatly affected by surface effects, as can be more than 5% for an irradiation with or without a bolus). seen for the CRT and IMRT breast cases (varying from 1.04 The exemplary DVH of a patient with three concentric to 1.25 in Table 3 and similar results for the outer SIB vol- head and neck target volumes in Fig. 1 depicts the same ume in Table 4). problem. Application of a 5 mm bolus changes the course of the PTV curve drastically at the low dose limb of the To compare IMRT results with earlier CRT results and to DVH. Obviously, minor changes in the placement of the assure continuity with respect to former dose prescription, bolus would influence a prescription based on D of the another substitute for ICRU RD must be provided. PTV PTV, although only the peripheral PTV areas are affected. D and PTV D (or D ...) may be reported as addi- Similarly, D depends clearly on further parameters. Cen- 95 min 01 95 tional information to describe the homogeneity of the tral volumes in our clinical practice tend to have much dose in the PTV. It should be noted that neither the dose lower D to ICRU RD ratios (1.040%, see Table 4) in con- below the D is restricted to the peripheral PTV areas nor trast to 107.0% and 106.9% for single or circumferential is the depth of a drastic dose reduction below the D PTVs. A prescription and reporting based on central areas restricted by using this prescription and reporting (CTV, PTV ) would be much more insensitive with respect method. Therefore, usage of D alone, can neither guar- to effects of surface and volume delineation variations. antee a certain lower limit for a tumour control probabil- ity nor "an expected clinical outcome of the treatment" This article is not intended to determine whether a [1]. Dose prescription and description of the plan quality D (PTV) or a D (PTV ) prescription would be the bet- 95 mean x cannot be achieved with a single parameter. An ASTRO/ ter method to prescribe tumour control. Both require AAPM working group recommends three DVH-points to more information about the low dose parts in relevant describe biologically relevant PTV-data of a dose distribu- areas that limit the tumour control probability (TCP) and tion [16]. Two of the points form the lower and upper hot spots that increase the probability of irreversible dam- dose limits, the third point should provide the dose "that age to healthy tissue. The D (PTV ) approach implies mean x covers the target" [16]. However, also mean and median additional information on the local behaviour of the dose doses in the PTV or PTV seem to be appropriate candi- distribution that is lost in the D concept: as can be seen x 95 dates to describe the "typical" dose, some of them much below, D (PTV ) together with additional information mean x Page 8 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 Table 4: Correlation of prescriptions (non-breast IMRT subgroups - topological aspects) denominator\numerator PTV PTV PTV ICRU ICRU D D D RD RD Mean Mean 95 (Case-Mean) [%] [%] [%] [%] [%] Single PTV PTV D 99.5 100.7 94.1 100.6 100.6 Median n = 12 0.3 0.4 1.9 1.3 2.4 PTV D 101.2 94.6 101.1 101.1 Mean 0.6 1.8 1.4 2.5 PTV D 93.4 99.9 99.9 5 Mean 2.1 1.3 2.4 PTV D 107.0 107.0 2.8 3.5 Central PTV PTV D 100.0 101.0 96.5 100.4 100.4 Median n = 15 0.3 0.8 0.7 0.8 1.6 PTV D 100.9 96.5 100.4 100.4 Mean 0.8 0.8 0.9 1.6 PTV D 95.6 99.4 99.4 5 Mean 1.3 0.8 1.6 PTV D 104.0 104.0 1.4 2.0 Circumferential PTV PTV D 99.9 100.0 93.6 100.0 100.0 Median n = 20 1.3 1.2 2.4 2.2 3.4 PTV D 99.8 93.4 99.8 99.8 Mean 2.0 2.7 2.9 3.9 PTV D 93.8 99.7 99.7 5 Mean 2.4 1.6 2.9 PTV D 106.9 106.9 4.2 5.0 Correlation of several prescription and reporting methods for subgroups of IMRT plans (non-breast cases) without surface effects (with bolus and PTV-distance to patient outline > 5 mm). All methods report for the same dose distribution per study. The upper value in each cell is the mean value; the lower value is the corresponding standard deviation. ICRU RD: ICRU Reference Dose; PTV : PTV shrunk by 5 mm; Case mean: Mean value of four (IMRT with a single PTV: five) points suitable for dose description according to ICRU 50/62. Central and circumferential volumes together form the volumes of SIB (2 or 3 nested volumes) like the standard deviation of the dose distribution allows should be noted, that the standard deviations of the mean linkage to a more biologically based evaluation (see last doses in the PTV and the PTV (σ /D in Table 1) are x D mean section). comparable for single PTV IMRT and CRT plans. This means that the fluctuations of the dose in PTV or PTV as Dose fluctuations in the target a whole are comparable for CRT and this special type of The fluctuations of the ICRU RD increase for IMRT as pre- IMRT (IMRT based on the DMPO optimization). Con- dicted by several authors [7]: the standard deviation for versely, the standard deviations of the ICRU RD from sev- the ICRU RD is slightly larger for IMRT plans than for the eral chosen points tend to be smaller for CRT plans than CRT techniques, and all correlations of other methods are for IMRT plans ("PTV D " and "PTV D " in Table 2, mean 5 mean weaker for IMRT than for CRT (the standard deviation of 3 and 4, last column "ICRU RD"). Perhaps this can be the quotient of the reported results is larger). However, it interpreted as if dose fluctuations of classical CRT plans Page 9 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 cannot compensate a potential underdosage at the pla- teau. This effect depends clearly on the dose difference of inner and outer volumes and could be relevant for dose differ- ences of 10% and more; the overestimation of the plateau dose could exceed 3% if the CTV mean dose would be used. For PTV D an underdose to the peripheral areas and an mean overdose to the inner areas could compensate each other. But this effect depends on the geometry of each individual E tative evaluation) with t tially Figure 1 xample abutting the patient outline of a head and n heree ck IM adR jacent, nested targ T case (not used for qua ets, par- nti- case, as can be deduced from the higher standard devia- Example of a head and neck IMRT case (not used for tions of PTV D (Table 4, circumferential volumes), mean quantitative evaluation) with three adjacent, nested indicating overestimations and underestimations that targets, partially abutting the patient outline. DVH for compensate each other averaging PTV D over all irradiation with 6 MV photons and bolus (thickness 5 mm): mean patients. PTV avoids both problems. dashed line. Without bolus: solid line. Left diagram: Three x nested, adjacent, non-overlapping PTV. Right diagram: Three nested PTV (PTV shrunk by 5 mm). From left to right: Outer SIB with nested volumes with a thickness of less than or (circumferential) to inner (central) PTV. equal 2× form no dose plateau in the outer PTV (such vol- umes were not addressed within this work). These SIB cases cannot be described by a concept equivalent to ICRU were less concentrated in the areas that were typically cho- points, because no point can be found which would be sen for ICRU Reference Points. This underlines the representative for this volume. Such volumes are mostly requirement of a volume integrating prescription and described by their minimal dose or concepts like D , D 99 98 reporting method for IMRT, even for rather homogeneous etcetera. IMRT plan types as used in this work. Adding a bolus to a breast plan changes the PTV mean It should be noted that the homogeneity of IMRT plans dose with respect to the ICRU reference dose by 2%. This has continuously increased in the past few years. For head is due to surface effects that should actually not influence and neck as well as related cases an extensive exploration the prescription, which should be based on the dose of data from the first IMRT decade had been performed within the central dose plateau with the highest accumu- [3]. Published DVHs (between 1990 and 1998) for realis- lation of tumour cells. Furthermore, dose calculation tic cases including scatter and absorption σ was 3.3% up algorithms tend to create erroneous results at the patient to 11% of a target with more than 5 mm to the patient surface. Obviously a dose of 0% as can be seen in table 1 outline, the related mean value of comparable non-IMRT for CRT breast cases is absurd. This topic will not be rotational techniques was 3.1%, classical opposed fields addressed here in detail, but clearly such areas should be with electrons reached 6% which should be compared to omitted when important values as the prescription dose of the dose in PTV which are a mean of 2.2% for σ are to be determined. Similar changes of the PTV mean D 5 reached for DMPO in head and neck cases in this work. dose can be expected due to delineation effects of the PTV Sliding window or volumetric arc techniques should be shape [17,18]. The same observation can be made in the able to create even more homogeneous dose distribu- example from Fig. 1: mean values of the central plateau of tions. These results also encourage the use of "non-D " each target (PTV ) are not affected by using a bolus or not 95 5 plans, but prescription and reporting methods with a con- (right side), whereas manifestly the mean dose of the PTV version factor around 1.00 in relation to the hitherto valid itself significantly changes. ICRU RD, if CRT and IMRT plans should be compared. In non-SIB cases PTV could resemble CTV, which then SIB and surface effects of the PTV and CTV mean dose could be alternatively used for prescription and reporting. The mean dose to the CTV for the outer SIB volumes over- However, CTVs with points near the surface should be estimated the plateau dose by 2% (in some cases almost chosen with caution. As can be seen in the case of the tis- 4%). For these outer PTVs of SIB, the dose gradient sue of the mammary gland for slender patients, CTV towards the inner PTVs influences the mean dose of the sometimes approaches the outline more closely than 5 outer PTV. It raises the mean dose in the CTV, pretending mm. The choice of 5 mm is due to the fact that these 5 mm a higher dose as actually reached in the dose plateau, often are used in daily practice (i.e. Fogliata 2005) [13]. whereas the dose overkill near the inner gradient probably Page 10 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 $ $ $ % % % $ $ $ # # # " " " ! ! ! ! " # $ % $  ! " # $ % $  ! " # $ % $ centr Figure 2 Correlation of several prescrip ICRU 52/60 Reference Dose cr al part of the PTV) tion and repo iteria) with the ratio of th rting methods (all related to e prescriptions PTV ICRU RD, the D /ICRU RD (PTV mean value of 4 or 5 points fulfilling t D : mean dose for the he 5 mean 5 mean Correlation of several prescription and reporting methods (all related to ICRU RD, the mean value of 4 or 5 points fulfilling the ICRU 52/60 Reference Dose criteria) with the ratio of the prescriptions PTV D /ICRU 5 mean RD (PTV D : mean dose for the central part of the PTV). Results for all plans of the study. All methods report for 5 mean the same dose distribution per study. Circles: All IMRT plans and related volumes. Triangles: All CRT plans used in this study. left: PTV D vs. PTV D (dose to 95% of the PTV). middle: PTV D vs. PTV D . (median dose for the PTV) right: 5 mean 95 5 mean median PTV D vs. PTV D (mean dose of the PTV). 5 mean mean In summary, only median dose in the PTV and the mean This is not necessarily so for a D prescription - not even dose to the PTV remain in contention to be the worthy in the majority of cases. If a prescription point ought to be successor of the ICRU RD. Both were mutually strongly defined, it should be placed at the border of the PTV near correlated (standard deviation of the quotient of about to the steep dose gradients. (Only for IMRT plans with 1%) and could be converted using a factor of 1.00. dose gaps in the centre of the PTV- that is for bad plans - a reference dose point representing the prescription dose Additional advantages and disadvantages of the mean could be placed somewhere in the central PTV area.) dose in PTV The definition of PTV includes the set of all points which In contrast to the prescription and reporting based on the can be chosen as ICRU Reference Points as a subset. Per- median dose which is regarded as a relevant method, the haps, PTV could even be interpreted as the set of all mean value of PTV could be a base for later biological x x points that could possibly be chosen as ICRU Reference interpretations with diverse biological models [5,14]. Points. Therefore, the close correlation to the special Brahme demonstrated that the pair of mean value and choice of ICRU Reference Points in this work is not sur- standard deviation σ of the dose in a volume with con- prising. The x = 5 mm margin ensures that all points are stant tumour cell density provides the possibility of the within a dose plateau and not near to the steep dose gra- subsequent approximate recalculation of tumour control dient at the borders of the PTV. In several cases, PTV probabilities or equivalent doses with arbitrary biological includes about 58% (32% to 73%) of the PTV volume for models [19]. (PTV is a better approximation of such a vol- the CRT and 41% (7% to 77%) for the IMRT cases. Fur- ume than PTV with its much smaller tumour cell densities thermore, all the excluded voxels are supposed to have a in the periphery.) Bleher et al. calculated a σ correction lower tumour cell density than the centre of the PTV, of the tumour control probability for a known "homoge- which includes the CTV. Due to the mean value theorem neous dose" probability curve TCP(D) [20]: for integration, the mean value of PTV can be represented by one or more points within the plateau PTV of the PTV. 2 (1a) TCP(D )=⋅ TCP() D exp(−k() D⋅s ) eff D Page 11 of 13 (page number not for citation purposes) Radiation Oncology 2009, 4:44 http://www.ro-journal.com/content/4/1/44 The first non-trivial non-zero term of a Taylor-series Conclusion around D = D (PTV ) with "The dose to the patient", formerly represented by the mean x ICRU Reference Point, continues to play a prominent role in daily practice (i.e. the doctor's letter). In contrast the ⎡ 2 ⎤ TCP ’(D)−⋅ TCP(D) TCP ’’(D) intended additional values in ICRU 62 [2], the expanded kD () = ⎢ ⎥ . (1b) ⎢ ⎥ TCP() D framework of these recommendations, sometimes tend to ⎣ ⎦ be in the background - all the more reason that a careful and coherent definition of this dose term is performed. The definition of PTV additionally allows the evaluation of D of the dose in the central PTV area - PTV - and the min x As successor for the ICRU Reference Point, equally usable standard deviation σ of the dose therein. Both are useful for IMRT and CRT, the authors recommend the median to control the dose homogeneity in the most important dose to the PTV or - preferably - the mean dose to the part of the PTV. For the whole PTV, potential dose inho- PTV , the central plateau. Both are "near" to the physical mogeneities in the centre are covered by the dominating dose distribution and provide a consistent extension of dose inhomogeneities at the periphery, which is caused by the ICRU Reference Dose (strong correlation and conver- uncertainties of the PTV definition or uncertainties in the sion factor ≈ 1.00). Mean doses to CTV and PTV do not to dose calculation (dose grid, surface effects). Therefore, such an extent. Usage of PTV D adds the possibility of D and σ of the PTV are less meaningful than D and x mean min D min using of the standard deviation in the PTV for later evalu- σ of the CTV or PTV . Such information - PTV D and D x x min ation of tumour control probabilities. Moreover it pro- σ - is routinely used in our clinic for automatic control of vides further parameters, which control the homogeneity these aspects of plan quality. In our institution, σ < 3.3% of the target (like standard deviation and minimal dose to is striven for to avoid relevant TCP-reductions due to the central plateau). inhomogeneity. For γ = 3 (the steepness of TCP-curve) and σ < 3.5% Brahme estimated a decrease of 5% for the TCP. Competing interests The authors declare that they have no competing interests. An additional advantage of the mean dose in the PTV is the additivity of mean doses in contrast to median doses Authors' contributions or D , albeit the biologically equivalent doses cannot KB was responsible for the primary concept and the simply be summed up. design of the study; he compiled the results and drafted the manuscript; MO evaluated most of the results; MG Some limitations of the D (PTV ) concept should not mean x critically accompanied the study and revised the manu- be concealed. For example for stereotactic treatments, script; MF was responsible for the patients, reviewed dose inhomogeneity may be intended. This inhomogene- patient data and revised the manuscript. All authors read ity is not arbitrary. The hot spots for small volumes are and approved the final manuscript. preferably in the central CTV. Commonly minimal doses (D with small y) in the CTV and PTV together with 100-y Acknowledgements maximum doses (D with small z) are reported. All these This work was in part supported by the German Research Foundation prescription values are relevant. Nevertheless even in the (Deutsche Forschungsgemeinschaft - DFG Project Code DFG BR 3460/2). case of stereotactic irradiations, a wider plateau with steep gradient near the PTV edge and a sharply peaked dose dis- This work was in part used for oral presentation at the 11th World Con- tribution with less steep gradient could be delivered with gress on Medical Physics and Biomedical Engineering, Munich 2009. the same specific data as stated above, although the former dose distribution would obviously provide the References better TCP. The additional use of D (PTV ) would 1. ICRU: Prescribing, recording, and reporting photon beam mean x therapy. In ICRU report Volume 50. Bethesda: International Commis- reveal the differences of both plans. sion on Radiation Units and Measurements; 1993. 2. 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Acta Radiol Oncol 1984, 23:379-391. 20. Bleher M, Bratengeier K, Richter J: Assessment of radiotherapy plans: dose-volume histograms, integral effects and tumor control. Strahlenther Onkol 1991, 167:220-226. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 13 of 13 (page number not for citation purposes)

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