Radiotherapy and Oncology xxx (2014) xxx–xxx
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Original article
In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance Giovanna Dipasquale ⇑, Philippe Nouet, Michel Rouzaud, Angèle Dubouloz, Raymond Miralbell, Thomas Zilli Department of Radiation Oncology, Geneva University Hospital, Switzerland
a r t i c l e
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Article history: Received 27 August 2013 Received in revised form 9 April 2014 Accepted 27 April 2014 Available online xxxx Keywords: Anal cancer Rectal cancer VMAT In vivo dosimetry CBCT
a b s t r a c t Objective: To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Methods: Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. Results: A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25–2.02 Gy) and 1.82 Gy (range, 0.19–2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, 0.11/ +0.19 Gy, p = 0.102) (median difference of 1.1%, range 6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., 8.9%). Conclusions: Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2014) xxx–xxx
New radiotherapy (RT) techniques, such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc technique (VMAT), are nowadays available to most centers. Together with the implementation of image-guided radiation therapy (IGRT) technologies, allowing planning target volume (PTV) reduction and sparing of healthy tissues and organs at risk (OARs) [1], such techniques have been introduced for the treatment of several tumor sites, including pelvic tumors. In ano-rectal cancer treatments, several studies have shown a dosimetric advantage of these techniques in sparing normal tissues close to the target volume [2–5]. Moreover, clinical outcome in terms of tumor control and toxicity profiles are encouraging and give support to the new treatment techniques as a standard of care in the treatment of these tumors [6–10]. Using highly precise and conformal RT techniques, pretreatment Quality Assurance (QA) protocols are recommended to ⇑ Corresponding author. Address: Department of Radiation Oncology, Geneva University Hospital, CH-1211 Geneva 14, Switzerland. E-mail address: [email protected] (G. Dipasquale).
ensure that the planned dose is correctly delivered to the target volume [11,12]. Recently, going further in the concept of QA, Mijnheer et al. stated that ‘‘all treatments with curative intent should be verified through in vivo dose measurements in combination with pre-treatment checks’’ [13]. Thermoluminescent dosimeters (TLDs) represent a reliable measuring tool, extensively used for measurements in anthropomorphic phantoms to investigate such techniques, for QA and to test the reliability of predictive dose algorithms [11,14–16]. Nevertheless, few attempts have been made to verify in vivo dose distributions in the target volume and/or in the OARs during conformal or intensity-modulated photon plans [13,17–23]. Difficulties in measuring the dose inside a patient cavity and also in identifying the dosimeter position in high-dose gradients regions, where small displacements can correspond to large dose variations are a likely explanation for this lack of data. In the treatment of anal cancer, we already used TLD dose measurements at the anal verge to assess the target dose delivery using three-dimensional conformal RT [24]. However, to our knowledge, no study has yet analyzed the
http://dx.doi.org/10.1016/j.radonc.2014.04.014 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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IGRT in vivo TLD dosimetry ano-rectal cancer
intracavitary dose distribution to the target volume during a VMAT treatment of anal and/or rectal cancer. The aim of this study was to assess intracavitary in vivo dose distribution using TLDs and cone-beam computed tomography scans (CBCTs) for QA of VMAT plans in patients with anal or rectal cancer. Materials and methods Eleven consecutive patients with anal (n = 9) or rectal cancer (n = 2) treated curatively in our institution from January 2012 through March 2013 using a VMAT technique, were investigated in this study for in vivo dosimetry (IVD) with TLDs, as routinely performed in our clinical practice for QA purposes [24]. Patient and treatment characteristics Patients with anal cancer were treated with RT and concomitant mytomicin-C and 5-fluorouracil chemotherapy, while patients with rectal cancer were treated with neoadjuvant chemo-RT with daily capecitabine before surgical resection. Patient demographics and disease characteristics are summarized in Table 1. The prescribed dose for anal cancer patients was 36 Gy in 20 fractions of 1.8 Gy to the anal lesion and elective lymph nodes regions, followed by a boost of 23.4 Gy in 1.8 Gy per fraction delivered to the anal tumor and the pathologically involved nodes. Rectal tumors were treated with a simultaneous integrated boost technique (SIB) delivering 25 fractions of 2 Gy (total dose 50 Gy) and 1.8 Gy (total dose 45 Gy) to the gross tumor volume (GTV) and the elective pelvic regions, respectively. Three-mm-thick computed tomography (CT) slices were acquired for planning purposes from the second–third lumbar vertebra or the iliac crests to 1/3 of the proximal femur. Anal cancer patients were lying supine with a hip and feet immobilization device, CombiFix™ (Civco Medical Solutions, Kalona, IA), while rectal cancer patients were lying prone using a belly board, Pelvic Prone Board™ (Macromedics, Netherlands). They were all instructed to fill the bladder just after emptying it by drinking 600–700 cc of water one hour before simulation and each treatment session. Delineation of target volumes and OAR was performed on a treatment planning system (TPS; Eclipse™ version 10, Varian Medical Systems, Palo Alto, CA). The GTV was defined using the 18F-deoxyglucose positron emission tomography images obtained in the simulation position or with the help of pelvic MR images co-registered with the planning CT slices. Elective clinical target volumes and pelvic normal tissues were contoured based on published Radiation Therapy Oncology Group consensus panel atlases [25,26]. To define the PTV the clinical target volume was expanded with a 3D isotropic margin of 7 mm. Table 1 Patient characteristics (n = 11). Median age (range)
67 (50–80)
Male/female (ratio)
4/7 (0.36)
Tumor location Anal canal ± margin Rectum
9 2
Histologic type Squamous cell carcinoma Adenocarcinoma
9 2
AJCC clinical stage T2 T3 T4 N+
5 5 1 3
Abbreviations: AJCC = American Joint Commission Cancer.
Seven patients were treated on a Varian Linac equipped with a Millennium 120 multi-leaf collimator (MLC) and 4 patients on a Novalis TX with a High Definition Millennium HD120 MLC. Both linear accelerators are equipped with on-board imaging systems (OBI). The VMAT technique (RapidArcÒ, Varian Medical Systems, Palo Alto, CA) consisted of 2 axial coplanar, single isocenter, full rotations arcs, delivered with a 6 MV photon energy beam. To minimize the tongue and groove effect, the collimator rotations were set to 30° and 330° respectively for each field, independently from the type of MLC. Dose calculations were performed using the analytic anisotropic algorithm (AAA) [27–30] implemented in the Eclipse™ version 10 TPS (Varian Medical Systems, Palo Alto, CA), with a calculation grid size of 0.25 cm. Patients were treated with daily 2D kilo-Voltage (kV) image guidance using the OBI system and weekly kV CBCTs. Once the CBCT was acquired and matching performed, the patient was automatically repositioned via table shifts and treated. Based on the institutional imaging protocol, translational displacements larger than 1 mm in any direction and rotations larger than 0.5° as compared to the reference simulation CT images were corrected. Pre-treatment in phantom plan QA Pre-treatment checks were performed with portal vision tools, PortalVision™ (Varian Medical Systems, Palo Alto, CA), and the 2D-ARRAY-seven29 with the OctaviusÒ phantom (PTW-Freiburg, Germany). The gamma criterion of 3 mm and 3% (distance to agreement and dose difference, respectively) was used for the analysis. TLD dosimetry and image guidance To perform intracavitary IVD, we employed the GR200AÒ TLDs (FIMEL, France) [31,32]. Their characteristics and calibration conditions are presented in Table 2. Multiple simultaneous point measurements, with single TLD per point, were performed to take into account possible large spatial dose variation. A median of 5 TLDs (range, 3–8) per patient were fitted in an endorectal probe with a diameter of 8 mm (Unomedical, ConvaTec, UK). Starting from the tip of the probe each TLD was inserted inside the catheter, by cutting along its length, and spaced from each other by 2 or 2.5 cm of wax filling material. Nevertheless for one patient, in order to quantify TLDs’ reading reproducibility in treatment conditions 2 TLDs were closely packed together, coupled per point of measurement, for a total of 4 measuring points and 8 TLDs. Fig. 1 represents a typical rectal probe used in this study. The endorectal probe was inserted with a protective sheet in the patient ano-rectal cavity. Image guidance with CBCT was undertaken thereafter prior to treatment. Using the CBCT images, TLDs were geographically located inside the patient, as shown in Fig. 2. After image fusion between the CBCT and the planning CT
Table 2 Thermoluminescent dosimeter (TLD) characteristics and calibration set up. Commercial name Material Shape Dimensions Usable dose range Dose calibration Linear dose range Sub-linear dose range Calibration energy Calibration set up in water equivalent phantom TLD reader TLD annealing procedure
GR200A LiF: Mg, Cu, P Cylindrical Chip Ø 4.5 mm 0.8 mm 0.5 lGy–12 Gy 2 Gy Up to 3 Gy From 3 Gy 6 MV SSD = 95 cm, depth 5 cm, field size 15 15 cm2 FIMEL PCL3 240 °C for 40 min
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
G. Dipasquale et al. / Radiotherapy and Oncology xxx (2014) xxx–xxx
Fig. 1. Measuring probe composed of a standard endorectal catheter housing thermoluminescent dosimeters packed between wax filling elements.
images, the expected dose at the center of each TLD was obtained by viewing the original dose distribution on the CBCT image blended with the planning CT and compared with the measured one during the treatment session (Fig. 3). For measurements at the anal margin (n = 6), a single TLD was packed in plastic and placed in regard of the tumor lesion involving the perianal skin. To quantify the reading contribution due to the kV-X-Rays of the CBCT image on the total TLD dose, five TLDs were fitted in the pelvic area of an anthropomorphic phantom, Rando™ (The Phantom Laboratory, Salem, NY) and irradiated with the same CBCT pelvic protocol (125 kVp, 80 mA, 13 ms, 360° gantry rotation) used in the study. TLD readings were converted into a megavoltage dose by using the clinical megavoltage X-ray beam TLD calibration curve. All TLD measurements were read within 24 h after irradiation and corrected for the corresponding daily linac output dose variation. Measurement accuracy and action level To define an action level for which deviations between measured and planned doses are considered significant, we first determined the overall accuracy of our measurement procedure. Using single point TLD measurements, we estimated an overall procedure accuracy of 7.7% in terms of 2 Standard Deviations (SD).
3
Fig. 3. Example of the planned dose viewed on a cone-beam computed tomography (CBCT) image blended with the planning CT, with visible rectal probe and thermoluminescent dosimeters. Measured doses, corrected for CBCT readings contribution, are also illustrated.
This accuracy level was obtained by propagating in quadrature several uncertainties (1SD): 3% for signal TLD reproducibility, 2% for TPS AAA algorithm dose calculation accuracy [14,33] and 1.4% for absorbed dose determination uncertainty when using the Swiss high energy photon therapy dosimetry protocol (http://ssrpm.ch/ r08hip-e.pdf). The daily change of the linac dose output was neglected in the overall accuracy calculation because we corrected each measurement for the daily linac output variation. The action level was set to the accuracy level. Measurements failing the action level set were investigated individually, using pre-treatment QA information and CBCT data looking for possible anatomical changes as compared to simulation. Per patient, we accepted only a single measurement point out of tolerance if considered not clinically relevant. On the other hand, even small but systematic differences between estimated and measured dose would not be accepted, because of underlying over or under dosage to large anatomical areas. Statistical analysis A comparison between measured and calculated doses was done using the Wilcoxon matched-pair signed rank-test with a threshold for statistical significance of p 6 0.05. All statistical tests
Fig. 2. Example of image fusion between the cone-beam computed tomography image and the corresponding computed tomography planning image.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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IGRT in vivo TLD dosimetry ano-rectal cancer
were two-sided and were performed using SPSS 17.0 statistic software package (SPSS, Inc. Chicago, IL).
.3
#
.25
Results
Gamma agreement index results were better than 95% for all plans tested in this study, both for portal vision tools and in phantom measurements. The analyses were carried out on points falling within the isodose reference surface of 10% of maximum dose in the measurement plan.
12 10
.15
8 6
.1
4
.05
2 0
0
TLD readings in the Rando™ Phantom The TLD readings in the phantom after irradiation with a standard pelvis CBCT protocol resulted in a mean ± standard deviation value of 0.02 ± 0.00 Gy, the equivalent of approximately 1% of the prescribed dose. This value was obviously subtracted from TLD measurements performed during treatment. CT dose index (CTDI) measurements were performed according to Hyer et al. [34] to verify that the dose given by the two OBI systems during a pelvis CBCT was equivalent. Doses on the central axis showed a difference of less than 2%, not appreciable on CBCT TLD readings. TLD dose readings in patients A total of 61 measurements (52 and 9 for patients with anal and rectal cancer, respectively) were analyzed, with 55 performed intracavitarily using an image guidance technique. Six TLDs were placed on the GTV located at the anal verge in the perianal skin and analyzed separately. Differences between expected and measured absolute doses were expressed in terms of percentage of the prescribed dose as more clinically relevant. The median planned and measured absolute doses for all intracavitary measurements were 1.81 Gy (range, 0.25–2.02 Gy with only 3 values lower than 1.7 Gy) and 1.82 Gy (range, 0.19– 2.12 Gy), respectively (p = 0.102). This corresponded in percentage of the prescribed dose to a 100% (range, 13.9–106.7%) and a 99.4% (range, 10.6–111.1%) for the calculated and measured values, respectively (p = 0.103). TLD absolute dose measurements differed from the planned ones by a median dose of 0.02 Gy, (range, 0.11/ +0.19 Gy), corresponding in percentage of prescribed doses to 1.1% median (range, 6.1%/+10.6%) when compared to the calculated doses. Differences >+7.7% between the measured and the calculated doses were observed for 3 measurement points (5% of all readings) within 3 patients, with 1 measurement over >10%. Regarding the measurements at the anal verge made without CBCT image guidance (n = 6), the median calculated and measured absolute doses were 1.75 Gy (range, 1.75–1.83 Gy) and 1.74 Gy (range, 1.59–1.84 Gy), respectively, or in terms of prescribed doses 97.5% (range, 97.2–101.7%) and 96.9% (range, 88.3–102.2%) for planned and measured values, respectively. TLD measurements differed by a median dose of 0.02 Gy (range, 0.16–0.08 Gy) compared with dose calculations, that is within ±7.7% of prescribed dose, except for one measurement at 8.9%. Fig. 4 shows the histogram of the frequency of the differences (measured planned) in percentage of the prescribed dose plotted with a bin size of 2%. TLD dose readings’ reproducibility The dose regions where each couple of TLDs was positioned presented a maximal dose variation of 1% in relation to the prescribed dose, i.e., 0.018 Gy. The mean standard deviation calculated per couple TLD measurements was 0.018 Gy (range,
16 14
.2
Rel.Freq.
Pre-treatment in phantom plan QA
18
-16
-12
-8 -4 0 4 8 12 (Measured-planned)/PrescribedDose(%)
16
Fig. 4. Histogram representing the frequency of the ratio ((measured planned)/ prescribed dose) for all measurements performed (intracavitary and perianal skin). The Y axis scale on the left represents the relative frequency while the Y axis on the right of the plot reports the number of events per bin. The bin size was set to 2%.
0.010–0.025 Gy) showing that in terms of dose prescription the degree of reproducibility of the TLDs was within 2%. To take into account the small sample size of this subgroup analysis, a TLD dose uncertainty of 3% was used. Discussion Implementation of IVD at the beginning of a RT treatment may permit to detect incorrect dose delivery to the target volume or OARs. Indeed, phantom plan pre-treatment QA verifications of highly modulated plans evaluate only a correct machine delivery and planning process, without considering the variability due to the patient anatomy and treatment reproducibility. On the other hand, IVD takes into account the complete planning procedure and may reveal potential errors in the planning process, in changes in the patient anatomy, or in patient misalignment errors with respect to treatment beams. All these elements can negatively compromise the clinical results of the treatment. The importance of IVD for QA purposes in the modern era of IMRT has been recently demonstrated in the treatment of prostate cancer by three published studies. Wertz et al. [17], measured rectal doses from IMRT for prostate cancer using an ionization chamber positioned with the aid of a kV X-ray taken before an IMRT fraction. The authors observed dose differences of at least 10% in about 30–35% of subjects. Den et al. [21] implanted some dosimeters directly in the prostate to measure the dose delivered to the target during IMRT. They showed that for 3 out of 20 patients dose deviations larger than 6% were correlated not to prostate misalignment, but to significant anatomic changes within the treated region. Hsi et al. [22] used TLDs to monitor rectal doses during proton therapy. In their study, it is worth to mention, they dropped two patients because of inadvertent large inter-fractional displacement of the rectal balloon in use, as seen on CT scans and pointed out by IVD. In the treatment of gynecologic tumors, Cilla et al. [23] presented a study implementing the use of endocavitary IVD for IMRT treatments by means of an ionization chamber inserted in a vaginal applicator. Three radio-opaque markers were implanted in the applicator to aid in daily repositioning of the target volume (upper two-thirds of the vaginal vault) via megavoltage portal images. Single point dose measurements per beam and per fraction (dose prescription of 6 Gy in 5 fractions) were performed, with 100% of the ratios measured/planned doses equal to 1 within 10%, on a beam per beam analysis. In this study an excellent control of the target volume, reproducibility of ionization chamber readings
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
G. Dipasquale et al. / Radiotherapy and Oncology xxx (2014) xxx–xxx
and a good plan delivery, led to ratios between measured and predicted total dose within 2% for all 6 patients. To our knowledge, no study implementing the use of intracavitary IVD and image guidance has been previously published for ano-rectal tumors treated with intensity-modulated techniques. In association with 3D in vivo electronic portal imaging (EPID) transit dosimetry, the concept of using CBCT images for IVD purposes was already used in 2008 by McDermott et al. [35]. In their study, they clearly showed the importance of CBCT to acquire 3D anatomical data to correlate with IVD results for the QA of hypofractionated IMRT for rectal cancer. CBCT images of a gas pocket in the rectum, though not frequent (1 fraction for 1 of the 9 analyzed patients) allowed, together with IVD, not only to estimate a region of over-dosage up to 4.5% but also to localize it with respect to the target volume. Other published studies for ano-rectal cancer exist but concern conformal treatments: Hayne et al. [19] measured radiation dose directly in the ano-rectum for pelvic 3-D radiotherapy using diodes, Weber et al. [24] measured the dose at the anal verge with TLDs and Scarantino et al. [18] used an implantable radiation metal oxide semiconductor field effect transistor dosimeter. Therefore, restricting to intracavitary IVD ano-rectal measurements only, excluding the study of Hsi et al. [22], as these authors worked with a different dose gradient pattern from photons IMRT because of protons, and the study of McDermott et al. [35], because using EPID dosimetry, our results are comparable to the intracavitary ano-rectal measurement data of Wertz et al. [17]. In their study a single measurement was taken at a specific point aiming to assess a steep gradient dose region in the rectum to be spared during the IMRT treatment. A CBCT – CT image matching was performed after the treatment session in order to evaluate patient position and the measured dose. Compared to the above technique, we believe that ours presents several advantages in improving the quality of the in vivo dose verification. First, our method succeeded to obtain simultaneously multiple dose measurements in a single treatment session; second, this procedure is easy to implement in routine clinical practice, helping for a good patient compliance with no extra-time required for treatment and no additional imaging doses. The total time to perform IVD per patient was approximately 1 h: 30 min to prepare the endorectal probe, 20 min to unpack and read the TLDs and 10 min to estimate the expected TLD doses using the CBCT images on the TPS. In our study, after fusion of the CBCT with inserted TLDs and planning CT, we estimated the expected dose by viewing the original dose distribution onto the CBCT image blended on the planned CT. We did not attempt to measure dose at pre-defined position as this may introduce additional errors with respect to TLD placement and therefore with the original dosimetry. This may explain the good correlation between measured and calculated doses with median differences of 0.02 Gy, (i.e., 1.1%) and 95% of measured points within ±7.7%. These findings are comparable with Wertz et al. [17] observations showing that if the patient positioning error is small (65 mm in all directions), the dose deviations remain within a mean value of ±6.5%. In three different patients a single difference larger than 7.7% was observed between the measured and the calculated dose. These measurements were not visually associated with anatomical changes on the CBCT as compared to simulation, with projected doses on the CBCT in a radius of 5-mm around the TLD center or with pre-treatment QA plan analysis results. To explain these dose disagreements, it also seems plausible to consider that some changes in the anatomy took place in time between the CBCT image and the treatment session delivery. However, as the onbeam treatment time using two VMAT arcs was approximately 2 min, much shorter than the 15 min to deliver a 9-field IMRT plan as reported by Wertz et al. [17], possible probe displacements or
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anatomy changes were minimized in our study. Consequently we considered not necessary to acquire new CBCT images at the end of the session for verification. Finally, as dose discrepancies were all located within the PTV in clinically non-critical areas and were all in the order of +10% of the prescription doses, these measurements were not repeated as the clinical impact was considered minimal. As concerning the dosimeter methodology used in our study, we believe that TLDs have several advantages compared to ionization chambers used in the study of Wertz et al. [17]: a smaller detector volume, 0.013 cm3, compared to 0.1 cm3 (i.e., 1/10th of the volume used by an ionization chamber); the inert material; the tissue equivalence that creates little interference with beam irradiation and therefore allows all types of irradiation techniques; a good visibility of the TLDs with the absence of related artifacts on CBCT datasets. Nevertheless, TLDs are not recommended if measurements need to be more precise than ±3% [36]. Concerning the perianal margin readings, only 1 measurement was superior to ±7.7%, though not exceeding ±10%, in opposition to our previous report by Weber et al., where we measured dose deviations as compared to the central axis prescribed dose of at least 10% in 26% of patients [24]. We believe that this difference may be explained by a better image quality and patient positioning with kV X-Rays imaging in use nowadays. It is noteworthy to mention that a good correlation between the calculated and the delivered dose is very important in the treatment of anal cancer, as the late ano-rectal function may be strongly influenced by the ‘‘real’’ dose delivered to the anal area. As we previously observed, patients with a lower mean difference in the anal TLD dose present a better anal function as compared for cases with larger deviations [24]. In conclusion, when checking for patient set-up reproducibility and organ motion as detected on CBCT, our QA protocol showed early in the treatment no major anatomical changes and a correct VMAT dose delivery. Moreover we showed that in target IVD for ano-rectal cancer is feasible to implement. Dose monitoring throughout the treatment course will be the next step for a personalized adaptive treatment. Conflicts of interest The author and co-authors have no potential conflict of interest to declare. References [1] Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer 2007;7:949–60. [2] Vieillot S, Azria D, Lemanski C, et al. Plan comparison of volumetric-modulated arc therapy (RapidArc) and conventional intensity-modulated radiation therapy (IMRT) in anal canal cancer. Radiat Oncol 2010;5:92. [3] Clivio A, Fogliata A, Franzetti-Pellanda A, et al. Volumetric-modulated arc radiotherapy for carcinomas of the anal canal: A treatment planning comparison with fixed field IMRT. Radiother Oncol 2009;92:118–24. [4] Richetti A, Fogliata A, Clivio A, et al. Neo-adjuvant chemo-radiation of rectal cancer with volumetric modulated arc therapy: summary of technical and dosimetric features and early clinical experience. Radiat Oncol 2010;5:14. [5] Duthoy W, De Gersem W, Vergote K, et al. Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer. Int J Radiat Oncol Biol Phys 2004;60:794–806. [6] Bazan JG, Hara W, Hsu A, et al. Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal. Cancer 2011;117:3342–51. [7] Mitchell MP, Abboud M, Eng C, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for anal cancer: outcomes and toxicity. Am J Clin Oncol 2013. PMID: 23466576, [e-Pub 3/4/2013]. [8] Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:1981–7.
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[22] Hsi WC, Fagundes M, Zeidan O, Hug E, Schreuder N. Image-guided method for TLD-based in vivo rectal dose verification with endorectal balloon in proton therapy for prostate cancer. Med Phys 2013;40:051715. [23] Cilla S, Macchia G, Digesu C, et al. Endocavitary in vivo dosimetry for IMRT treatments of gynecologic tumors. Med Dosim 2011;36:455–62. [24] Weber DC, Nouet P, Kurtz JM, Allal AS. Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry. Radiother Oncol 2001;59:39–43. [25] Gay HA, Barthold HJ, O’Meara E, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys 2012;83:e353–62. [26] Myerson RJ, Garofalo MC, El Naqa I, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 2009;74:824–30. [27] Ulmer W, Harder D. A triple Gaussian pencil beam model for photon beam treatment planning. Z Med Phys 1995;5:25–30. [28] Ulmer W, Harder D. Applications of a triple Gaussian pencil beam model for photon beam treatment planning. Z Med Phys 1996;6:68–74. [29] Ulmer W, Kaissl W. The inverse problem of a Gaussian convolution and its application to the finite size of the measurement chambers/detectors in photon and proton dosimetry. Phys Med Biol 2003;48:707–27. [30] Fogliata A, Nicolini G, Vanetti E, Clivio A, Cozzi L. Dosimetric validation of the anisotropic analytical algorithm for photon dose calculation: fundamental characterization in water. Phys Med Biol 2006;51:1421–38. [31] Muniz JL, Delgado A. A study of LiF GR-200 for radiotherapy mailed dosimetry. Phys Med Biol 1997;42:2569–76. [32] Fill U, Regulla DF. Use of Chinese LiF:Mg, Cu, P (GR-200) TL Detectors at therapy-level absorbed doses. Appl Radiat Isot 1998;49:791–3. [33] Ding GX, Duggan DM, Lu B, et al. Impact of inhomogeneity corrections on dose coverage in the treatment of lung cancer using stereotactic body radiation therapy. Med Phys 2007;34:2985–94. [34] Hyer DE, Hintenlang DE. Estimation of organ doses from kilovoltage conebeam CT imaging used during radiotherapy patient position verification. Med Phys 2010;37:4620–6. [35] McDermott LN, Wendling M, Nijkamp J, et al. 3D in vivo dose verification of entire hypo-fractionated IMRT treatments using an EPID and cone-beam CT. Radiother Oncol 2008;86:35–42. [36] Low DA, Moran JM, Dempsey JF, Dong L, Oldham M. Dosimetry tools and techniques for IMRT. Med Phys 2011;38:1313–38.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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Original article
In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance Giovanna Dipasquale ⇑, Philippe Nouet, Michel Rouzaud, Angèle Dubouloz, Raymond Miralbell, Thomas Zilli Department of Radiation Oncology, Geneva University Hospital, Switzerland
a r t i c l e
i n f o
Article history: Received 27 August 2013 Received in revised form 9 April 2014 Accepted 27 April 2014 Available online xxxx Keywords: Anal cancer Rectal cancer VMAT In vivo dosimetry CBCT
a b s t r a c t Objective: To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Methods: Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. Results: A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25–2.02 Gy) and 1.82 Gy (range, 0.19–2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, 0.11/ +0.19 Gy, p = 0.102) (median difference of 1.1%, range 6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., 8.9%). Conclusions: Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2014) xxx–xxx
New radiotherapy (RT) techniques, such as intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc technique (VMAT), are nowadays available to most centers. Together with the implementation of image-guided radiation therapy (IGRT) technologies, allowing planning target volume (PTV) reduction and sparing of healthy tissues and organs at risk (OARs) [1], such techniques have been introduced for the treatment of several tumor sites, including pelvic tumors. In ano-rectal cancer treatments, several studies have shown a dosimetric advantage of these techniques in sparing normal tissues close to the target volume [2–5]. Moreover, clinical outcome in terms of tumor control and toxicity profiles are encouraging and give support to the new treatment techniques as a standard of care in the treatment of these tumors [6–10]. Using highly precise and conformal RT techniques, pretreatment Quality Assurance (QA) protocols are recommended to ⇑ Corresponding author. Address: Department of Radiation Oncology, Geneva University Hospital, CH-1211 Geneva 14, Switzerland. E-mail address: [email protected] (G. Dipasquale).
ensure that the planned dose is correctly delivered to the target volume [11,12]. Recently, going further in the concept of QA, Mijnheer et al. stated that ‘‘all treatments with curative intent should be verified through in vivo dose measurements in combination with pre-treatment checks’’ [13]. Thermoluminescent dosimeters (TLDs) represent a reliable measuring tool, extensively used for measurements in anthropomorphic phantoms to investigate such techniques, for QA and to test the reliability of predictive dose algorithms [11,14–16]. Nevertheless, few attempts have been made to verify in vivo dose distributions in the target volume and/or in the OARs during conformal or intensity-modulated photon plans [13,17–23]. Difficulties in measuring the dose inside a patient cavity and also in identifying the dosimeter position in high-dose gradients regions, where small displacements can correspond to large dose variations are a likely explanation for this lack of data. In the treatment of anal cancer, we already used TLD dose measurements at the anal verge to assess the target dose delivery using three-dimensional conformal RT [24]. However, to our knowledge, no study has yet analyzed the
http://dx.doi.org/10.1016/j.radonc.2014.04.014 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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IGRT in vivo TLD dosimetry ano-rectal cancer
intracavitary dose distribution to the target volume during a VMAT treatment of anal and/or rectal cancer. The aim of this study was to assess intracavitary in vivo dose distribution using TLDs and cone-beam computed tomography scans (CBCTs) for QA of VMAT plans in patients with anal or rectal cancer. Materials and methods Eleven consecutive patients with anal (n = 9) or rectal cancer (n = 2) treated curatively in our institution from January 2012 through March 2013 using a VMAT technique, were investigated in this study for in vivo dosimetry (IVD) with TLDs, as routinely performed in our clinical practice for QA purposes [24]. Patient and treatment characteristics Patients with anal cancer were treated with RT and concomitant mytomicin-C and 5-fluorouracil chemotherapy, while patients with rectal cancer were treated with neoadjuvant chemo-RT with daily capecitabine before surgical resection. Patient demographics and disease characteristics are summarized in Table 1. The prescribed dose for anal cancer patients was 36 Gy in 20 fractions of 1.8 Gy to the anal lesion and elective lymph nodes regions, followed by a boost of 23.4 Gy in 1.8 Gy per fraction delivered to the anal tumor and the pathologically involved nodes. Rectal tumors were treated with a simultaneous integrated boost technique (SIB) delivering 25 fractions of 2 Gy (total dose 50 Gy) and 1.8 Gy (total dose 45 Gy) to the gross tumor volume (GTV) and the elective pelvic regions, respectively. Three-mm-thick computed tomography (CT) slices were acquired for planning purposes from the second–third lumbar vertebra or the iliac crests to 1/3 of the proximal femur. Anal cancer patients were lying supine with a hip and feet immobilization device, CombiFix™ (Civco Medical Solutions, Kalona, IA), while rectal cancer patients were lying prone using a belly board, Pelvic Prone Board™ (Macromedics, Netherlands). They were all instructed to fill the bladder just after emptying it by drinking 600–700 cc of water one hour before simulation and each treatment session. Delineation of target volumes and OAR was performed on a treatment planning system (TPS; Eclipse™ version 10, Varian Medical Systems, Palo Alto, CA). The GTV was defined using the 18F-deoxyglucose positron emission tomography images obtained in the simulation position or with the help of pelvic MR images co-registered with the planning CT slices. Elective clinical target volumes and pelvic normal tissues were contoured based on published Radiation Therapy Oncology Group consensus panel atlases [25,26]. To define the PTV the clinical target volume was expanded with a 3D isotropic margin of 7 mm. Table 1 Patient characteristics (n = 11). Median age (range)
67 (50–80)
Male/female (ratio)
4/7 (0.36)
Tumor location Anal canal ± margin Rectum
9 2
Histologic type Squamous cell carcinoma Adenocarcinoma
9 2
AJCC clinical stage T2 T3 T4 N+
5 5 1 3
Abbreviations: AJCC = American Joint Commission Cancer.
Seven patients were treated on a Varian Linac equipped with a Millennium 120 multi-leaf collimator (MLC) and 4 patients on a Novalis TX with a High Definition Millennium HD120 MLC. Both linear accelerators are equipped with on-board imaging systems (OBI). The VMAT technique (RapidArcÒ, Varian Medical Systems, Palo Alto, CA) consisted of 2 axial coplanar, single isocenter, full rotations arcs, delivered with a 6 MV photon energy beam. To minimize the tongue and groove effect, the collimator rotations were set to 30° and 330° respectively for each field, independently from the type of MLC. Dose calculations were performed using the analytic anisotropic algorithm (AAA) [27–30] implemented in the Eclipse™ version 10 TPS (Varian Medical Systems, Palo Alto, CA), with a calculation grid size of 0.25 cm. Patients were treated with daily 2D kilo-Voltage (kV) image guidance using the OBI system and weekly kV CBCTs. Once the CBCT was acquired and matching performed, the patient was automatically repositioned via table shifts and treated. Based on the institutional imaging protocol, translational displacements larger than 1 mm in any direction and rotations larger than 0.5° as compared to the reference simulation CT images were corrected. Pre-treatment in phantom plan QA Pre-treatment checks were performed with portal vision tools, PortalVision™ (Varian Medical Systems, Palo Alto, CA), and the 2D-ARRAY-seven29 with the OctaviusÒ phantom (PTW-Freiburg, Germany). The gamma criterion of 3 mm and 3% (distance to agreement and dose difference, respectively) was used for the analysis. TLD dosimetry and image guidance To perform intracavitary IVD, we employed the GR200AÒ TLDs (FIMEL, France) [31,32]. Their characteristics and calibration conditions are presented in Table 2. Multiple simultaneous point measurements, with single TLD per point, were performed to take into account possible large spatial dose variation. A median of 5 TLDs (range, 3–8) per patient were fitted in an endorectal probe with a diameter of 8 mm (Unomedical, ConvaTec, UK). Starting from the tip of the probe each TLD was inserted inside the catheter, by cutting along its length, and spaced from each other by 2 or 2.5 cm of wax filling material. Nevertheless for one patient, in order to quantify TLDs’ reading reproducibility in treatment conditions 2 TLDs were closely packed together, coupled per point of measurement, for a total of 4 measuring points and 8 TLDs. Fig. 1 represents a typical rectal probe used in this study. The endorectal probe was inserted with a protective sheet in the patient ano-rectal cavity. Image guidance with CBCT was undertaken thereafter prior to treatment. Using the CBCT images, TLDs were geographically located inside the patient, as shown in Fig. 2. After image fusion between the CBCT and the planning CT
Table 2 Thermoluminescent dosimeter (TLD) characteristics and calibration set up. Commercial name Material Shape Dimensions Usable dose range Dose calibration Linear dose range Sub-linear dose range Calibration energy Calibration set up in water equivalent phantom TLD reader TLD annealing procedure
GR200A LiF: Mg, Cu, P Cylindrical Chip Ø 4.5 mm 0.8 mm 0.5 lGy–12 Gy 2 Gy Up to 3 Gy From 3 Gy 6 MV SSD = 95 cm, depth 5 cm, field size 15 15 cm2 FIMEL PCL3 240 °C for 40 min
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
G. Dipasquale et al. / Radiotherapy and Oncology xxx (2014) xxx–xxx
Fig. 1. Measuring probe composed of a standard endorectal catheter housing thermoluminescent dosimeters packed between wax filling elements.
images, the expected dose at the center of each TLD was obtained by viewing the original dose distribution on the CBCT image blended with the planning CT and compared with the measured one during the treatment session (Fig. 3). For measurements at the anal margin (n = 6), a single TLD was packed in plastic and placed in regard of the tumor lesion involving the perianal skin. To quantify the reading contribution due to the kV-X-Rays of the CBCT image on the total TLD dose, five TLDs were fitted in the pelvic area of an anthropomorphic phantom, Rando™ (The Phantom Laboratory, Salem, NY) and irradiated with the same CBCT pelvic protocol (125 kVp, 80 mA, 13 ms, 360° gantry rotation) used in the study. TLD readings were converted into a megavoltage dose by using the clinical megavoltage X-ray beam TLD calibration curve. All TLD measurements were read within 24 h after irradiation and corrected for the corresponding daily linac output dose variation. Measurement accuracy and action level To define an action level for which deviations between measured and planned doses are considered significant, we first determined the overall accuracy of our measurement procedure. Using single point TLD measurements, we estimated an overall procedure accuracy of 7.7% in terms of 2 Standard Deviations (SD).
3
Fig. 3. Example of the planned dose viewed on a cone-beam computed tomography (CBCT) image blended with the planning CT, with visible rectal probe and thermoluminescent dosimeters. Measured doses, corrected for CBCT readings contribution, are also illustrated.
This accuracy level was obtained by propagating in quadrature several uncertainties (1SD): 3% for signal TLD reproducibility, 2% for TPS AAA algorithm dose calculation accuracy [14,33] and 1.4% for absorbed dose determination uncertainty when using the Swiss high energy photon therapy dosimetry protocol (http://ssrpm.ch/ r08hip-e.pdf). The daily change of the linac dose output was neglected in the overall accuracy calculation because we corrected each measurement for the daily linac output variation. The action level was set to the accuracy level. Measurements failing the action level set were investigated individually, using pre-treatment QA information and CBCT data looking for possible anatomical changes as compared to simulation. Per patient, we accepted only a single measurement point out of tolerance if considered not clinically relevant. On the other hand, even small but systematic differences between estimated and measured dose would not be accepted, because of underlying over or under dosage to large anatomical areas. Statistical analysis A comparison between measured and calculated doses was done using the Wilcoxon matched-pair signed rank-test with a threshold for statistical significance of p 6 0.05. All statistical tests
Fig. 2. Example of image fusion between the cone-beam computed tomography image and the corresponding computed tomography planning image.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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IGRT in vivo TLD dosimetry ano-rectal cancer
were two-sided and were performed using SPSS 17.0 statistic software package (SPSS, Inc. Chicago, IL).
.3
#
.25
Results
Gamma agreement index results were better than 95% for all plans tested in this study, both for portal vision tools and in phantom measurements. The analyses were carried out on points falling within the isodose reference surface of 10% of maximum dose in the measurement plan.
12 10
.15
8 6
.1
4
.05
2 0
0
TLD readings in the Rando™ Phantom The TLD readings in the phantom after irradiation with a standard pelvis CBCT protocol resulted in a mean ± standard deviation value of 0.02 ± 0.00 Gy, the equivalent of approximately 1% of the prescribed dose. This value was obviously subtracted from TLD measurements performed during treatment. CT dose index (CTDI) measurements were performed according to Hyer et al. [34] to verify that the dose given by the two OBI systems during a pelvis CBCT was equivalent. Doses on the central axis showed a difference of less than 2%, not appreciable on CBCT TLD readings. TLD dose readings in patients A total of 61 measurements (52 and 9 for patients with anal and rectal cancer, respectively) were analyzed, with 55 performed intracavitarily using an image guidance technique. Six TLDs were placed on the GTV located at the anal verge in the perianal skin and analyzed separately. Differences between expected and measured absolute doses were expressed in terms of percentage of the prescribed dose as more clinically relevant. The median planned and measured absolute doses for all intracavitary measurements were 1.81 Gy (range, 0.25–2.02 Gy with only 3 values lower than 1.7 Gy) and 1.82 Gy (range, 0.19– 2.12 Gy), respectively (p = 0.102). This corresponded in percentage of the prescribed dose to a 100% (range, 13.9–106.7%) and a 99.4% (range, 10.6–111.1%) for the calculated and measured values, respectively (p = 0.103). TLD absolute dose measurements differed from the planned ones by a median dose of 0.02 Gy, (range, 0.11/ +0.19 Gy), corresponding in percentage of prescribed doses to 1.1% median (range, 6.1%/+10.6%) when compared to the calculated doses. Differences >+7.7% between the measured and the calculated doses were observed for 3 measurement points (5% of all readings) within 3 patients, with 1 measurement over >10%. Regarding the measurements at the anal verge made without CBCT image guidance (n = 6), the median calculated and measured absolute doses were 1.75 Gy (range, 1.75–1.83 Gy) and 1.74 Gy (range, 1.59–1.84 Gy), respectively, or in terms of prescribed doses 97.5% (range, 97.2–101.7%) and 96.9% (range, 88.3–102.2%) for planned and measured values, respectively. TLD measurements differed by a median dose of 0.02 Gy (range, 0.16–0.08 Gy) compared with dose calculations, that is within ±7.7% of prescribed dose, except for one measurement at 8.9%. Fig. 4 shows the histogram of the frequency of the differences (measured planned) in percentage of the prescribed dose plotted with a bin size of 2%. TLD dose readings’ reproducibility The dose regions where each couple of TLDs was positioned presented a maximal dose variation of 1% in relation to the prescribed dose, i.e., 0.018 Gy. The mean standard deviation calculated per couple TLD measurements was 0.018 Gy (range,
16 14
.2
Rel.Freq.
Pre-treatment in phantom plan QA
18
-16
-12
-8 -4 0 4 8 12 (Measured-planned)/PrescribedDose(%)
16
Fig. 4. Histogram representing the frequency of the ratio ((measured planned)/ prescribed dose) for all measurements performed (intracavitary and perianal skin). The Y axis scale on the left represents the relative frequency while the Y axis on the right of the plot reports the number of events per bin. The bin size was set to 2%.
0.010–0.025 Gy) showing that in terms of dose prescription the degree of reproducibility of the TLDs was within 2%. To take into account the small sample size of this subgroup analysis, a TLD dose uncertainty of 3% was used. Discussion Implementation of IVD at the beginning of a RT treatment may permit to detect incorrect dose delivery to the target volume or OARs. Indeed, phantom plan pre-treatment QA verifications of highly modulated plans evaluate only a correct machine delivery and planning process, without considering the variability due to the patient anatomy and treatment reproducibility. On the other hand, IVD takes into account the complete planning procedure and may reveal potential errors in the planning process, in changes in the patient anatomy, or in patient misalignment errors with respect to treatment beams. All these elements can negatively compromise the clinical results of the treatment. The importance of IVD for QA purposes in the modern era of IMRT has been recently demonstrated in the treatment of prostate cancer by three published studies. Wertz et al. [17], measured rectal doses from IMRT for prostate cancer using an ionization chamber positioned with the aid of a kV X-ray taken before an IMRT fraction. The authors observed dose differences of at least 10% in about 30–35% of subjects. Den et al. [21] implanted some dosimeters directly in the prostate to measure the dose delivered to the target during IMRT. They showed that for 3 out of 20 patients dose deviations larger than 6% were correlated not to prostate misalignment, but to significant anatomic changes within the treated region. Hsi et al. [22] used TLDs to monitor rectal doses during proton therapy. In their study, it is worth to mention, they dropped two patients because of inadvertent large inter-fractional displacement of the rectal balloon in use, as seen on CT scans and pointed out by IVD. In the treatment of gynecologic tumors, Cilla et al. [23] presented a study implementing the use of endocavitary IVD for IMRT treatments by means of an ionization chamber inserted in a vaginal applicator. Three radio-opaque markers were implanted in the applicator to aid in daily repositioning of the target volume (upper two-thirds of the vaginal vault) via megavoltage portal images. Single point dose measurements per beam and per fraction (dose prescription of 6 Gy in 5 fractions) were performed, with 100% of the ratios measured/planned doses equal to 1 within 10%, on a beam per beam analysis. In this study an excellent control of the target volume, reproducibility of ionization chamber readings
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
G. Dipasquale et al. / Radiotherapy and Oncology xxx (2014) xxx–xxx
and a good plan delivery, led to ratios between measured and predicted total dose within 2% for all 6 patients. To our knowledge, no study implementing the use of intracavitary IVD and image guidance has been previously published for ano-rectal tumors treated with intensity-modulated techniques. In association with 3D in vivo electronic portal imaging (EPID) transit dosimetry, the concept of using CBCT images for IVD purposes was already used in 2008 by McDermott et al. [35]. In their study, they clearly showed the importance of CBCT to acquire 3D anatomical data to correlate with IVD results for the QA of hypofractionated IMRT for rectal cancer. CBCT images of a gas pocket in the rectum, though not frequent (1 fraction for 1 of the 9 analyzed patients) allowed, together with IVD, not only to estimate a region of over-dosage up to 4.5% but also to localize it with respect to the target volume. Other published studies for ano-rectal cancer exist but concern conformal treatments: Hayne et al. [19] measured radiation dose directly in the ano-rectum for pelvic 3-D radiotherapy using diodes, Weber et al. [24] measured the dose at the anal verge with TLDs and Scarantino et al. [18] used an implantable radiation metal oxide semiconductor field effect transistor dosimeter. Therefore, restricting to intracavitary IVD ano-rectal measurements only, excluding the study of Hsi et al. [22], as these authors worked with a different dose gradient pattern from photons IMRT because of protons, and the study of McDermott et al. [35], because using EPID dosimetry, our results are comparable to the intracavitary ano-rectal measurement data of Wertz et al. [17]. In their study a single measurement was taken at a specific point aiming to assess a steep gradient dose region in the rectum to be spared during the IMRT treatment. A CBCT – CT image matching was performed after the treatment session in order to evaluate patient position and the measured dose. Compared to the above technique, we believe that ours presents several advantages in improving the quality of the in vivo dose verification. First, our method succeeded to obtain simultaneously multiple dose measurements in a single treatment session; second, this procedure is easy to implement in routine clinical practice, helping for a good patient compliance with no extra-time required for treatment and no additional imaging doses. The total time to perform IVD per patient was approximately 1 h: 30 min to prepare the endorectal probe, 20 min to unpack and read the TLDs and 10 min to estimate the expected TLD doses using the CBCT images on the TPS. In our study, after fusion of the CBCT with inserted TLDs and planning CT, we estimated the expected dose by viewing the original dose distribution onto the CBCT image blended on the planned CT. We did not attempt to measure dose at pre-defined position as this may introduce additional errors with respect to TLD placement and therefore with the original dosimetry. This may explain the good correlation between measured and calculated doses with median differences of 0.02 Gy, (i.e., 1.1%) and 95% of measured points within ±7.7%. These findings are comparable with Wertz et al. [17] observations showing that if the patient positioning error is small (65 mm in all directions), the dose deviations remain within a mean value of ±6.5%. In three different patients a single difference larger than 7.7% was observed between the measured and the calculated dose. These measurements were not visually associated with anatomical changes on the CBCT as compared to simulation, with projected doses on the CBCT in a radius of 5-mm around the TLD center or with pre-treatment QA plan analysis results. To explain these dose disagreements, it also seems plausible to consider that some changes in the anatomy took place in time between the CBCT image and the treatment session delivery. However, as the onbeam treatment time using two VMAT arcs was approximately 2 min, much shorter than the 15 min to deliver a 9-field IMRT plan as reported by Wertz et al. [17], possible probe displacements or
5
anatomy changes were minimized in our study. Consequently we considered not necessary to acquire new CBCT images at the end of the session for verification. Finally, as dose discrepancies were all located within the PTV in clinically non-critical areas and were all in the order of +10% of the prescription doses, these measurements were not repeated as the clinical impact was considered minimal. As concerning the dosimeter methodology used in our study, we believe that TLDs have several advantages compared to ionization chambers used in the study of Wertz et al. [17]: a smaller detector volume, 0.013 cm3, compared to 0.1 cm3 (i.e., 1/10th of the volume used by an ionization chamber); the inert material; the tissue equivalence that creates little interference with beam irradiation and therefore allows all types of irradiation techniques; a good visibility of the TLDs with the absence of related artifacts on CBCT datasets. Nevertheless, TLDs are not recommended if measurements need to be more precise than ±3% [36]. Concerning the perianal margin readings, only 1 measurement was superior to ±7.7%, though not exceeding ±10%, in opposition to our previous report by Weber et al., where we measured dose deviations as compared to the central axis prescribed dose of at least 10% in 26% of patients [24]. We believe that this difference may be explained by a better image quality and patient positioning with kV X-Rays imaging in use nowadays. It is noteworthy to mention that a good correlation between the calculated and the delivered dose is very important in the treatment of anal cancer, as the late ano-rectal function may be strongly influenced by the ‘‘real’’ dose delivered to the anal area. As we previously observed, patients with a lower mean difference in the anal TLD dose present a better anal function as compared for cases with larger deviations [24]. In conclusion, when checking for patient set-up reproducibility and organ motion as detected on CBCT, our QA protocol showed early in the treatment no major anatomical changes and a correct VMAT dose delivery. Moreover we showed that in target IVD for ano-rectal cancer is feasible to implement. Dose monitoring throughout the treatment course will be the next step for a personalized adaptive treatment. Conflicts of interest The author and co-authors have no potential conflict of interest to declare. References [1] Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer 2007;7:949–60. [2] Vieillot S, Azria D, Lemanski C, et al. Plan comparison of volumetric-modulated arc therapy (RapidArc) and conventional intensity-modulated radiation therapy (IMRT) in anal canal cancer. Radiat Oncol 2010;5:92. [3] Clivio A, Fogliata A, Franzetti-Pellanda A, et al. Volumetric-modulated arc radiotherapy for carcinomas of the anal canal: A treatment planning comparison with fixed field IMRT. Radiother Oncol 2009;92:118–24. [4] Richetti A, Fogliata A, Clivio A, et al. Neo-adjuvant chemo-radiation of rectal cancer with volumetric modulated arc therapy: summary of technical and dosimetric features and early clinical experience. Radiat Oncol 2010;5:14. [5] Duthoy W, De Gersem W, Vergote K, et al. Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer. Int J Radiat Oncol Biol Phys 2004;60:794–806. [6] Bazan JG, Hara W, Hsu A, et al. Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal. Cancer 2011;117:3342–51. [7] Mitchell MP, Abboud M, Eng C, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for anal cancer: outcomes and toxicity. Am J Clin Oncol 2013. PMID: 23466576, [e-Pub 3/4/2013]. [8] Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:1981–7.
Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
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IGRT in vivo TLD dosimetry ano-rectal cancer
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Please cite this article in press as: Dipasquale G, Nouet P. In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.04.014
