|Ahead of print publication
A radiobiological and dosimetrical comparison between simultaneous integrated and sequential boost intensity-modulated arc treatment of locally advanced head-and-neck cancer
Abhijit Mandal1, Sunil Choudhary1, Nilesh Mani1, Sushil Kumar Aggarwal2
1 Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Varanasi, Uttar Pradesh, India
2 Department of Otorhinolaryngology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
|Date of Submission||26-Mar-2019|
|Date of Decision||07-Aug-2019|
|Date of Acceptance||20-Aug-2019|
|Date of Web Publication||28-Jan-2020|
Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Purpose: The study aimed to compare the radiobiological and dosimetric parameters between sequential boost (SEQB) and simultaneous integrated boost (SIB) treatment regimen using intensity-modulated arc therapy technique in locally advanced head-and-neck cancer (LAHNC) patients.
Materials and Methods: A total of 24 previously untreated LAHNC patients were randomized into SIB (n= 11) and SEQB (n = 13) arms. The planning computed tomography data set was transferred to the treatment planning system. All the target volumes and organ at risk volumes were delineated. Single plan for SIB group and three plans (three phases) were generated for SEQB group of patients. Radiobiological and dosimetric parameters were compared.
Results: The BED10(planned) value for high-risk (HR) planning target volume (PTV) was same in both groups, whereas for intermediate-risk (IR) PTV and low-risk (LR) PTV, the values were higher in SEQB arm than SIB arm. The V95 values were 100% for all the target volumes in both arms of patients. The average D100 value for gross target volume, HR PTV, and IR PTV was higher in SEQB arm than that in the SIB arm. The average D100 value for LR PTV was higher in the SIB arm compared to that of the SEQB arm. The BED10(achieved) was calculated using D100 values of target volumes. The difference of BED10(achieved) values between SEQB arm and SIB arm further increased than the BED10(planned) values for all target volumes. The maximum doses for spinal cord, spinal cord planning risk volume, and brain stem were within the tolerance dose in both groups of patients. The left and right parotid glands sparing was comparable in both groups of patients. Average integral dose was higher in the SIB group than SEQB group. The average total monitor unit per fraction was higher in the SEQB arm than that in the SIB arm.
Conclusion: SIB regimen may be considered as more logical and efficient over SEQB regimen in the treatment of LAHNC with comparable radiobiological and dosimetric parameters.
Keywords: Intensity-modulated arc therapy, rapid arc, simultaneous integrated boost, volumetric-modulated arc therapy
|How to cite this URL:|
Mandal A, Choudhary S, Mani N, Aggarwal SK. A radiobiological and dosimetrical comparison between simultaneous integrated and sequential boost intensity-modulated arc treatment of locally advanced head-and-neck cancer. J Can Res Ther [Epub ahead of print] [cited 2020 Feb 29]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=277101
| > Introduction|| |
Intensity-modulated arc therapy (IMAT/volumetric -modulated arc therapy/rapid arc) is now considered as a better choice of intensity-modulated radiotherapy treatment techniques in locally advanced head-and-neck cancer (LAHNC) patients.,, IMAT techniques have many salient advantageous features such as higher patient throughput, expenses of lower monitor units (MUs) and simplicity in treatment execution. The treatment delivery regimen may be in the form of sequential boost (SEQB) or simultaneous integrated boost (SIB). In the SEQB regimen, different plans are used for each phase of treatment, whereas in SIB regimen, a single plan is used throughout the course of treatment delivering differential doses to different target volumes [Figure 1]. SIB treatment plans further offer less treatment planning and treatment verification efforts than SEQB treatment plans. Some radiobiological merits (higher BED10 value for target volumes) are also observed in aggressive SIB treatment regimen. However, very less clinical data are available in the literature which compare radiobiological and dosimetric parameters between SIB and SEQB regimen and established correlation with clinical outcome in terms of disease control and normal tissue complications. A randomized study was designed to compare all radiobiological and dosimetrical parameters between two comparable SIB and SEQB regimens using the IMAT technique in LAHNC patients.
|Figure 1: Graphical representation of simultaneous integrated boost and sequential boost regimen|
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| > Materials and Methods|| |
A total of 24 previously untreated LAHNC (Stage III–Stage IVA) patients were included in this study. The patients were randomized into SIB and SEQB arms [Figure 2]. The planning computed tomography (CT) data set (3.75-mm slice thickness and 3-mm slice interval) was acquired in treatment position using GE light speed V 128 slice diagnostic CT scan unit. The CT data set was transferred to the Eclipse™ treatment planning system (Version 11.0.47). All the target volumes, i.e., gross target volume (GTV), high risk (HR), intermediate risk (IR), low risk (LR) planning target volume (PTV), and organ at risk (OAR) volumes were delineated by a single radiation oncologist.
The dose prescriptions of both arms are shown in [Table 1]. In [Table 2], the dose constraints were described. The highest optimization priority was given to target volumes, followed by serial OAR structures (spinal cord, spinal cord planning risk volume [PRV], and brain stem), followed by parallel OAR structures (parotids). In SEQB treatment arm, three plans were generated for three phases, and each phase was independently optimized. In the independent optimization, only OARs tolerance doses were distributed among phases according to phase weights. During independent optimization, the dose contribution of earlier phases was not considered, whereas a single treatment plan was generated using one time optimization in SIB group patients, delivering differential doses to the different target volume and sparing OARs. Two full rotation arcs with complimentary collimator angle (±30°) were used to generate the treatment plan for both groups of patients.
The plans were verified using portal dosimetry system attached with the treatment linear accelerator before treatment execution. All the patients were treated using 6 MV linear accelerator (Unique™ Performance, Varian Medical System).
| > Results|| |
Eleven patients in the SIB arm and 13 patients in the SEQB arm were enrolled in the study.
The BED10(planned) value for HR PTV was same (71.4) in both the groups, whereas for IR PTV and LR PTV, the values were 59.0 and 63.6 and 50.0 and 56.0 for SIB and SEQB arm, respectively [Table 3].
The target volume distributions were comparable in both groups of patients [Table 4]. Average overall treatment time for both groups of patients was also comparable (50.4 days and 50.3 days for SIB and SEQB groups, respectively).
The dose-volume histogram (DVH) of SIB plan and plan sum of SEQB three phases were analyzed [Figure 3].
|Figure 3: Typical dose-volume histogram of simultaneous integrated boost plan and sequential boost plan sum|
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The V95 values were 100% for all the target volumes in both arms of patients. The average D100 values for GTV, HR PTV, and IR PTV were higher [Table 5] in SEQB arm than in SIB arm (7066 cGy vs. 6900 cGy, 6720 cGy vs. 6497 cGy, and 6308 cGy vs. 5917 cGy). The average D100 values for LR PTV were 5037 cGy and 4871 cGy for SIB and SEQB arms, respectively.
BED10(achieved) values of each target volume were calculated using the respective average D100 values. It is observed that BED10(achieved) values were higher for all target volumes in SEQB arm than SIB arm. The BED10(achieved) values for GTV and HR PTV were 70.0 and 72.3 and 64.4 and 67.5 for SIB and SEQB, respectively, whereas for IR PTV and LR PTV, the values were 56.6 and 62.0 and 45.0 and 53.8 for SIB and SEQB arms, respectively. It is also observed that for all target volumes, the difference of achieved BED10 values between SEQB arm and SIB arm, further increased than the difference of planned BED10 values between SEQB arm and SIB arm [Figure 4] and [Table 6].
|Figure 4: BED10difference between sequential boost and simultaneous integrated boost arm (planned vs. achieved)|
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Maximum doses of the spinal cord, PRV spinal cord, and brain stem for all the patients were within the mentioned plan objectives for both groups of patients. The left and right parotid glands sparing (D [mean] <2600 cGy) was comparable in both groups of patients [Table 7]. In the SIB group, both parotid and single parotid were speared in four and one patients, respectively. In SEQB group, both parotid and single parotid were speared in four and one patients, respectively.
Average integral dose was 12.8% higher in the SIB group than that of the SEQB group. The average total MUs per fraction was 25.6% higher in the SEQB arm than that in the SIB arm.
| > Discussion|| |
The SIB treatment regimen offers logistically better, cost-effective, and lesser treatment uncertainty probabilities over the SEQB regimen.
To achieve equal tumor control in both groups of patients, BED10(planned) values for GTV and HR PTV were equated in both treatment regimens. A larger volume is irradiated in SIB treatment throughout the whole course of the treatment as compared to SEQB regimen where the irradiated volume is reduced phase by phase. Hence, it is expected that in the combination of chemotherapy and large volume irradiation of SIB arm, if the BED10 values of IR PTV and LR PTV were matched in both regimens, then it may increase the toxicity profile for the SIB group of patients. To balance the radiobiological volume effect, BED10(planned) values for IR PTV and LR PTV intentionally kept lower in the SIB arm.
In the SEQB, each phase was optimized independently, which cause higher D100 values for GTV, HR PTV, and IR PTV in the plan sum DVH than that in the SIB plans. If the interrelated optimization (dependent optimization) was performed for each phases, then only comparable D100 values for target volume may be observed in plan sum DVH. However, dependent optimization may lead to phase-wise inhomogeneous dose distribution within the various target volumes. D100 value of LR PTV is lower in SEQB arm as the prescription dose is much lesser than SIB arm (5000 cGy vs. 5400 cGy).
In a common scenario, LR PTV situated within IR PTV and IR PTV situated in HR PTV. In SEQB planning, some more doses added up to the LR PTV and IR PTV in flowing phases. By calculating BED10(achieved) values using average D100 values of target volumes, one can estimate the radiobiological effectiveness of each target volumes of each patient. Results show that the further increase of differences of BED10 values between SEQB and SIB group in the finally achieved and executed plans. Radiobiological optimization is used to get radiobiological equivalent treatment plan. Higher BED10(achieved) values for all target volumes in SEQB regimen may exhibit with higher tumor control in this group.
The patient's body mean dose multiplied with body volume (approximated as unit density body volume) is the integral dose. As large volume is irradiated throughout the treatment course in SIB arm, a clear increase in patient body mean dose is observed. Hence, higher integral dose may cause an increase in acute systemic normal tissue complication such as hematological toxicity in SIB group of patients.
In SIB single plan optimization, each target volume can be appropriately optimized. This effect facilitates to achieve a promising reduction in MUs per fraction in SIB treatment regimen than SEQB regimen. This factor may be considered as good merit of SIB regimen. The reduction in MUs per fraction will increase the higher patient throughput, lower the load in the treatment unit, and lesser the intra-fraction movement-related errors.
A small number of patients enrolled in this study may be considered as the main limitation to draw concrete conclusion as this effect further causes lacks rigorous statistical analysis.
An important question arises in this study, that for SEQB planning, should we go for independent optimization and get higher physical dose/radiobiological dose for different target volume in plan sum or one can proceed with dependent optimization and accept phase-wise inhomogeneity but get optimal target volume coverage and homogeneous distribution in plan sum. This question should be addressed properly.
| > Conclusion|| |
SIB regimen may offer more organizational benefits over SEQB regimen in the treatment of LAHNC with comparable radiobiological and dosimetric parameters. The clinical comparison may explore more pros and cons between SIB and SEQB regimens.
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Doornaert P, Verbakel WF, Bieker M, Slotman BJ, Senan S. RapidArc planning and delivery in patients with locally advanced head-and-neck cancer undergoing chemoradiotherapy. Int J Radiat Oncol Biol Phys 2011;79:429-35.
Brown ML, Glanzmann C, Huber G, Bredell M, Rordorf T, Studer G. IMRT/VMAT for malignancies in the head-and-neck region: Outcome in patients aged 80. Strahlenther Onkol 2016;192:526-36.
Moncharmont C, Vallard A, Guy JB, Prades JM, Rancoule C, Magné N, et al.
Real-life efficacy of volumetric modulated arc therapy in head and neck squamous cell carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis 2017;134:165-9.
Orlandi E, Palazzi M, Pignoli E, Fallai C, Giostra A, Olmi P, et al.
Radiobiological basis and clinical results of the Simultaneous Integrated Boost (SIB) in Intensity Modulated Radiotherapy (IMRT) for head and neck cancer: A review. Crit Rev Oncol Hematol 2010;73:111-25.
Miyazaki M, Nishiyama K, Ueda Y, Ohira S, Tsujii K, Isono M, et al.
Preliminary analysis of the sequential simultaneous integrated boost technique for intensity-modulated radiotherapy for head and neck cancers. J Radiat Res 2016;57:406-11.
Amin MB, Edge SB, Greene FL, et al
, eds. AJCC Cancer Staging Manual. 8th
ed. New York: Springer; 2017.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]