Dosimetric and radiobiological comparison of IMRT, VMAT, and Helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases

doi:10.21203/rs.3.rs-2465750/v1

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Research Article

Dosimetric and radiobiological comparison of IMRT, VMAT, and Helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases

https://doi.org/10.21203/rs.3.rs-2465750/v1

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Journal Publication

published 09 Jan, 2024

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Purpose

To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques.

Methods and Materials

In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30Gy and 36Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP.

Results

All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ±0.01,0.1 ±0.04, and 0.08 ±0.02 for IMRT, VMAT, and HT, respectively (P<0.05). The percentage of TCP for the PTV boost was 99.99±0.003, 99.98 ±0.004, and 99.99±0.002 of IMRT, VMAT, and HT, respectively, (P<0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies.

Conclusion

The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

TCP

NTCP

Whole brain radiation

SIB

Hippocampal Sparing

Metastatic brain tumour is the secondary tumour caused by the cancer cells which have travelled from different parts of the body to the brain, it could be single or multiple. Brain metastases (BM) originated from primary lung and breast cancer with 40–50% and 15–25%, respectively. 5–10% of brain metastases occur with the unknown primary site of cancer. [1].

Magnetic resonance imaging (MRI) is the preferred imaging modality for the assessment of BM [2]. The prognosis for BM is generally poor, with median survival rates ranging from one to a few years. Radiotherapy is an essential modality in the treatment of BM. However, neurocognitive deficit occurs due to both BM and radiotherapy [3].

Whole brain radiotherapy (WBRT) is used as a primary treatment modality to treat multiple brain metastases and it may also be used as a stand-alone treatment for the unresectable metastatic tumour. WBRT by parallel opposed fields is the standard palliative care for the BM and has a poor prognosis rate with survival rates of 3 to 6 months in many cases [4]. Advanced treatment modalities like intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) have highly conformal treatment delivery. These techniques can be used to deliver the whole brain treatment, and simultaneously a high dose can be delivered to the gross disease with minimal margins.

The hippocampus are small structures in the brain and plays a significant role in the limbic system. The hippocampus supports the retrieval of stored memories and the formation of new memories. Bilateral or unilateral damage to the hippocampus is known to cause learning changes and memory formation. Several studies have demonstrated that whole brain radiation therapy causes a significant decline in the neurocognitive function (NCF) [5, 6]. With the recent advancement in radiotherapy techniques, it is possible to have a WBRT with hippocampal sparing to avoid adverse effects.

The hippocampal avoidance whole brain radiotherapy is the technique that can reduce both the mean and maximum dose to the hippocampus for a prescription dose of 30 Gy in 10 fractions to the whole brain [7]. In comparison to historical data of patients treated with regular WBRT, the phase II-RTOG0933 trial on hippocampal avoidance whole brain radiotherapy for brain metastases found considerable memory preservation [8].

Modern RT techniques such as dynamic IMRT, VMAT, and HT can produce steep dose gradients between OAR and target volume. Also, we can give differential doses to the whole brain and brain metastases simultaneously with these techniques. The simultaneous integrated boost (SIB) method offers enhanced patient comfort due to an optimized dose distribution, reducing overall treatment time and expenses when compared to the sequential boost method. The dose heterogeneity for the whole brain volume increased by sparing the hippocampus while simultaneously boosting the metastases.

The aim of this study is to compare dosimetric and radiobiological parameters for modern radiotherapy techniques, such as IMRT, VMAT and HT in whole brain radiotherapy with simultaneous integrated boost with hippocampal sparing in multiple brain metastases.

2.1. Patient selection and imaging

The treatment data of twenty patients (14 male and 6 female) (aged between 43 and 86 years, mean 66.5 years) who received treatment for multiple brain metastases ranging from one to seventeen have been used in this study. All patients were simulated with all-in-one (AIO) solutions in the head-first supine position. A three-clamp thermoplastic mask was prepared to immobilize the patients. A kilovoltage computed tomography (CT) scan with slice thickness of 1.25 to 2.5 mm was acquired from the vertex to C5 vertebra to include the whole brain volume. Contrast enhanced magnetic resonance imaging (CEMRI) was registered to the planning CT images to delineate gross tumour volume (GTV) and organ at risk (OAR) structures.

The RTOG 0933 contouring atlas was used as a guideline to define the targets and organs at risk (OARs) in an eclipse treatment planning system (Varian Medical Systems, Palo Alto, USA). With the help of MRI and CT co-registered images, the gross tumour volumes (GTVs) and bilateral hippocampus were accurately contoured. The boost planning target volume (PTV boost) was created from GTVs using a 2mm isotopic margin. The hippocampus avoidance (HA) zone was created using a margin of 5mm from the hippocampus. The clinical target volume (CTV) has been created by delineating the entire brain. The whole brain planning target volume (PTV) was created from CTV using a 3 mm isotropic margin and cropping from the HA and boost volume. For planning comparison, OARs such as optic nerve, optic chiasm, brain stem, eye, lens, pituitary, parotid, and spinal cord were created. Additionally, three-ring structures were created by applying 3mm, 4mm, and 1cm margins from the total- hippocampus structure to achieve conformity in the whole brain PTV dose coverage. The PTV volumes, the number of boost volumes of individual patients, and the distance between boost volume and hippocampus have mentioned in table 1.

2.2. Treatment planning

All the plans were optimized with an aggregate dose of 30 Gy for PTV whole brain and simultaneously 36 Gy for PTV boost in 10 fractions using three planning proficiencies (HT, IMRT, and VMAT). The Eclipse treatment planning system (version 15.6, Varian, USA) has data configured for the 6 MV photon energy Varian TrueBeam accelerator, with an HD 120 Multi-Leaf Collimator (MLC) with 60 leaf pairs (with a spatial resolution of 0.25 cm in the centre and 0.5 cm in the periphery), had been used to create the VMAT and IMRT plans. An Anisotropic Analytical Algorithm (AAA) dose calculation model was used to calculate the dose after setting the calculation grid size to 2.5 mm.

Table 1: Patient wise OAR and PTV characteristics

Patient	No of boost volume	PTV Boost Volume (CC)	Hippocampus volume (CC)	Minimum distance between boost volume and hippocampus (mm)	PTV Whole Brain Volume (CC)
1	1	29.4	4.1	41	1239.7
2	10	212.8	6.8	10	1224.2
3	6	25.2	2.9	1	1336.8
4	3	97.3	6.6	10	1335.5
5	1	71.4	1.7	21	1270.7
6	2	143.1	1.4	6	1242.4
7	3	63.4	1.9	8	1734.1
8	1	103.1	10.8	10	1727.3
9	1	49.5	1.8	44	1375.1
10	17	30.2	3.2	5	1319.1
11	3	54.0	2.9	36	1443.6
12	2	10.3	2.2	20	1934.5
13	1	54.4	2.6	12	1601.2
14	3	33.3	3.4	16	1476.2
15	4	48.9	3.2	6	1331.1
16	2	18.5	2.0	50	1383.5
17	2	5.7	1.5	8	1801.9
18	5	117.3	4.6	14	1453.9
19	2	21.1	3.9	6	1426.8
20	1	24.6	2.4	56	1326.3

OAR-Organ at Risk, PTV-Planning Target Volume.

We have used eleven fields with nine coplanar equally spaced from 200 to 160 degree (collimator 90-degree, couch 0-degree) and two non-coplanar fields 310 and 335 degree (collimator 0-degree, couch 90 degree). We have used total four coplanar fields with two clock wise (CW180.1-179.9, collimator rotation 85 degree) and two counter clockwise (CCW 179.9-180.1, collimator rotation 95 degree).

The CT images and structure datasets were transferred to the precision workstation (version 3.3, precision, Accuray, USA) database via the DICOM RT protocol to create a HT plans. The field width of 2.5cm, modulation factor of 3, and the pitch value of 0.3 are the parameters used for optimization in the treatment planning workstation. The Radixact machine (Version X9, Accuray, USA) was selected as a treatment machine with 6 MV flattening filter-free photon energy with a dynamic jaw (Tomo edge) and 0.625cm resolution binary MLC in the treatment planning system. The final dose calculation has been performed using the collapsed cone convolution superposition (CCCS) algorithm for HT plans.

Table 2: Dose volume criteria of RTOG 0933 [9].

PTV/OAR	Criteria	Variation acceptable	Variation unacceptable
PTV whole brain volume	D_2%≤ 37.5Gy	D_2%≤ 40Gy	V_30Gy< 90%

	D_98%≥ 25Gy	D_98%< 25Gy	D_2%> 40Gy

Bilateral-Hippocampus	D_100%≤ 9Gy	D_100%≤ 10Gy	D_100%> 10Gy

	D_max≤ 16Gy	D_max≤ 17Gy	D_max≥ 17Gy

Optic Nerves and Optic Chiasm*	D_max≤ 37.5Gy	D_max≤ 37.5Gy	D_max≥ 37.5Gy

*Dmax is dose to 0.03cc volume of the organ at risk

D2%-Dose received by 2% of volume, D98%-Dose received by 98% of the volume, D100%-Dose received by 100% of the volume, Dmax-Maximum dose, V30Gy-volume covered by 30Gy isodose line.

We followed the RTOG 0933 planning criteria mentioned in table 2 in all three planning methods for whole brain PTV with hippocampal avoidance. The dose coverage of 95% of the target volume is covered with at least 95% of the prescription dose to boost volume. The PTV boost volume dose coverage was not compromised even though the boost volume falls near or inside the hippocampal avoidance region. Also, the optimization process was repeated until the OAR doses could be further reduced without compromising PTV coverage for all three techniques.

2.3. Dosimetric plan quality comparison

2.3.1Target Coverage analysis

The coverage of the PTV whole brain was analyzed by V30Gy (Volume covered by 30Gy isodose line), D2% (Dose received by 2% of PTV volume), and D98% (Dose received by 98% of PTV volume) as mentioned in table 2. The PTV boost was analyzed for D98% (Dose received by 98% of PTV volume), and the PTV whole brain and PTV boost were evaluated for their conformity index, coverage index, and homogeneity index (table 3) to identify and compare the plan quality.

2.3.2. Organ at risk analysis

The hippocampus dose was evaluated with maximum dose (Dmax), mean dose (Dmean), and D100% (Dose in 100% of volume). All other OARs like optic chiasm, brain stem, combined parotid, optic nerve, lens, and eye (Left & Right) doses were evaluated for Dmax and Dmean.

2.3.3. Radiobiological analysis

The TCP of both PTV whole brain and boost volume have been analyzed with Niemierko’s EUD model (Table 3) with the parameters TCD50=22.17Gy, γ50=3.6, a=-1, and α/β=10 [10]. The OARs have been analyzed with LKB model (Table 3) with the parameters mentioned in table 4.

2.4. Statistical analysis

Data statistics have been demonstrated as mean [±] standard deviation (SD). Radiobiological metrics and differences in the dosimetric parameters among the three plans have been analyzed through 2 tailed student t-test (IBM, SPSS_v24). P-value of less than 0.05 was regarded as statistically significant.

All the plans were evaluated based on the RTOG 0933 protocol criteria (table2) and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ±0.01,0.1 ±0.04, and 0.08 ±0.02 for IMRT, VMAT, and HT, respectively, (table 5) and the comparison between the plans is statistically significant (P<0.05). The percentage of volume covered by 30Gy dose to PTV whole brain were 92.5±1.62, 92.04±1.85, and 91.68±1.87, respectively, and the difference between the plan was not statistically significant. The parameters of PTV boost and PTV whole brain are mentioned in table4. The PTV boost and PTV whole brain dose coverage for all three plans for patient number 3 are shown in figure 1.

The dose to the 100% of volume (D100%) received by both left and right-side hippocampi has been displayed in figure 2, and it shows that HT plans received fewer doses compare to IMRT and VMAT plans. D100% of all three plans are adhered to the RTOG protocol values mentioned in table 2.

Table 3: Dosimetric and radiobiological equations for the plan comparison

Name	equations	Parameters required	References
Conformity index	{1}	PD = prescription dose to the PTV. PTV Vol = total PTV volume.	[11]
Homogeneity index	{2}	D₉₈%= dose received by 98% of PTV. D₂%= dose received by 2% of PTV. D₅₀%= dose received by 50% of PTV.
Coverage Index	{3}	Dmin = minimum dose received by PTV. PD = prescription dose received by PTV.
Equivalent Uniform Dose (EUD)	{4}	EQD_i = dose delivered to a sub volume V_i. a = unitless model parameter.	[12, 13]
Equivalent Uniform Dose (EUD)	{5}	Di = total dose received by the bin. nf = total number of fractions. α/β = parameters of the linear-quadratic model.	[12, 13]
Niemierko’s EUD model	{6}	γ50= a unit less model parameter describing the dose-response curve’s slope. TCD50=tolerance dose needed for controlling 50% of the tumour (if irradiated uniformly).	[13,14]
Lyman–Kutcher–Burman (LKB) model	{7}	TD50 = tolerance dose to produce 50% of complication of OARs (if uniformly irradiated). Vi = volume in a specific dose bin i. Di = dose given to each bin. m = dimensionless parameter for determining the slope of complication probability versus dose curve. n = volume dependence of the complication’s probability.	[15,16,17]

	{8}

Table 4: Parameters used for NTCP calculations [18,19]

Organ	n	m	TD₅₀ (Gy)	α/β	End point
Brain Stem	0.16	0.14	65	3	Necrosis
Lens*	0.3	0.27	18	1.2	Blindness
Eye*	0.2	0.19	65	3	Blindness
Optic nerve*	0.25	0.14	65	3	Blindness
Parotid*	0.7	0.18	28.4	3	Xerostomia
Hippocampus*	0.25	0.15	48	2	NCF decline

* Both left and right side.

NCF= neurocognitive function.

Table 5 Dosimetric comparison of planning target volume

		IMRT⁽ⁱ⁾		VMAT^(j)		HT^(K)		P -Value
	Parameters	Mean	SD	Mean	SD	Mean	SD	I vs j	I vs k	j vs k
PTV boost	Dmax (Gy)	39.32	0.92	39.20	1.22	39.81	0.86	0.73	0.08	0.07
	Dmean (Gy)	37.78	0.71	36.61	0.54	37.75	0.39	0.00	0.85	0.00
	HI	0.07	0.01	0.10	0.04	0.08	0.02	0.00	0.02	0.02
	CI	1.00	0.00	0.99	0.02	1.00	0.01	0.10	0.58	0.10
	Cov I	0.95	0.10	0.95	0.11	0.93	0.11	0.88	0.36	0.37

PTV whole brain	D30Gy (%)	92.50	1.62	92.04	1.85	91.68	1.87	0.31	0.17	0.46
	D2% (Gy)	34.23	0.82	34.97	0.62	33.83	0.53	0.00	0.08	0.00
	D98% (Gy)	26.38	1.08	26.63	0.72	26.28	0.68	0.35	0.74	0.04
	HI	0.25	0.04	0.26	0.03	0.24	0.03	0.31	0.69	0.02
	CI	0.96	0.01	0.96	0.01	0.96	0.01	0.59	0.13	0.30
	Cov I	0.47	0.08	0.47	0.05	0.45	0.13	0.81	0.00	0.64
	V90% (%)	97.42	0.90	97.70	0.59	97.64	0.33	0.36	0.23	0.59

IMRT=Intensity modulated radiotherapy, VMAT=Volumetric modulated arc therapy, HT=Helical tomotherapy, PTV=Planning target volume, Dmax=maximum dose to the PTV, Dmin=minimum dose to the PTV, Dmean=mean dose to the PTV, CI=Conformity Index, HI=Homogeneity index, Cov I=Coverage Index, V90%= 90% of dose covered by the percentage of PTV volume, D2%=Dose received by 2 percentage of volume, and D98%=Dose received by 98 percentage of volume.

Table 6 Equivalent uniform dose for organ at risk

Name	IMRT^(q)		VMAT^(r)		HT^(s)			P -Value
Name	Mean	SD	Mean	SD	Mean	SD	q Vs r	q Vs s	r Vs s
Parotid Rt	8.90	2.96	9.27	3.34	4.34	0.82	0.18	0.00	0.00
Parotid Lt	8.69	2.52	8.66	3.25	4.17	0.77	0.94	0.00	0.00
Total Hippocampal	8.09	0.63	8.73	0.58	8.22	0.78	0.00	0.40	0.00
Brain Stem	38.94	1.96	37.36	3.47	38.70	1.81	0.04	0.67	0.02
Spinal cord	30.66	7.79	28.27	8.59	28.95	8.32	0.02	0.08	0.30

IMRT=Intensity modulated radiotherapy, VMAT=Volumetric modulated arc therapy, HT=Helical tomotherapy.

The distance between the hippocampus is less than 1cm from the PTV boost, also more than three PTV boost volume patients, a total of eleven patients were separately analyzed for the maximum hippocampus dose (figure 3). Four patients had a higher maximum hippocampus dose when the distance was less between the PTV boost and the hippocampus compared with IMRT and VMAT plans.

The equivalent uniform dose (EUD) of the OARs like parotid, hippocampus, brain stem, and spinal cord are mentioned in table 6. The mean parotid dose of the left and right side, brain stem, and spinal cord are less for HT plans as compared to IMRT and VMAT plans. The comparison between plans (IMRT versus HT) and (VMAT versus HT) is statistically significant (P < 0.05) for parotid. Also, the comparison between (IMRT versus VMAT) and (VMAT versus HT) is statistically significant (P < 0.05) for hippocampus and brainstem.

The comparison between equivalent uniform doses for optic structures like the eye, lens, optic chiasm, and optic nerve has been shown in figure 4. The HT plan doses for optic structures are less than IMRT and VMAT plans, except for optic chiasm. Also, the optic structures receive higher doses by the VMAT plan when compared to the IMRT plan, except for the eye.

Figure 5 shows the comparison of the equivalent uniform dose of hippocampal left and right sides. The average EUD of the right and left hippocampus were 8.01Gy ±0.65, 8.74Gy ±0.66, 8.31Gy ± 1.0, 18.14Gy ±0.59, 8.68Gy ±0.50, and 7.99Gy ±0.61for IMRT, VMAT, and HT plans, respectively. The mean dose for the left-sided hippocampus was higher in the HT plan compared to the IMRT and VMAT. Also, the left-sided hippocampal doses were higher for patient number 3 on all three planning proficiencies, 9.76Gy, 10.79Gy, and 12.28Gy for IMRT, VMAT, and HT, respectively. These doses were higher because the location of the PTV boost volume was within 5mm of the left hippocampus.

The TCP of the PTV boost were 99.99%±0.003, 99.98% ±0.004, and 99.99%±0.002 of IMRT, VMAT, and HT, respectively, and the comparison between IMRT versus VMAT and VMAT versus HT are statistically significant (P<0.005). Also, the TCP of PTV whole brain was 92.42%±11.86, 97.24% ±3.6, and 93.98%±3.8 for IMRT, VMAT, and HT, respectively, and the comparison between the plans is not statistically significant.

The NTCP of the OARs was evaluated with the LKB model, and found that the HT plans have lesser value compared to IMRT and VMAT plans, except for optic chiasm. The NTCP value of the left and right lenses were higher with the VMAT plan compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies, and the NTCP value is higher for the brain stem and spinal cord in the IMRT plan when compared to VMAT and HT plans (Figure 6).

The IMRT, VMAT, and HT are the techniques that have established roles for hippocampal sparing in whole-brain radiation therapy. The study result of Gondi et al. shows that we can reduce 87% and 81% of hippocampal doses using HT and LINAC-based IMRT techniques, respectively. The authors also commented that it is challenging to spare the hippocampus while delivering a simultaneous boost with whole-brain irradiation [20].

Recently, Popp et al. [21] conducted a study between WBRT and HA-WBRT techniques for a cohort of 48 and 35 patients, respectively. Their study showed average atrophy of 3.1% with HA-WBRT compared to 8.5% with conventional WBRT in the first two years after radiotherapy.

We have studied the possibility of sparing the hippocampus and other OARs while performing the WBRT and simultaneous boost with the three planning methods and compare these plans with dosimetric, EUD, and radiobiological models. Balasubramanian et al. [22,23] compared photon and proton planning radiobiologically using LKB and Niemierko NTCP models, and they found that the results were reliable for comparing different planning methods.

The use of the HT delivery technique for hippocampal avoidance of WBRT with SIB has been investigated by Gutierrez et al. [24]. Also, they compared dosimetric parameters of different treatment plans as a function of the field width (FW) and pitch value. They found that smaller FW can improve the homogeneity to the WBRT and reduce mean eye dose. Also, the mean dose to the hippocampus was unchanged among the different pitch values and FW.

F.Hus et al. studied the VMAT delivery technique for hippocampal avoidance of WBRT with SIB in patients with one to three metastases [25]. They discovered that the VMAT technique could deliver WBRT efficiently while conformally limiting the hippocampus dose and simultaneously delivering radio surgical equivalent doses to selected metastases. Gondi et al. [26] addressed the problem of hippocampus avoidance during WBRT in a comprehensive hypothesis paper. They found that the risk of therapeutic failure due to relapse or progression in the hippocampus sub-granular zone, however, is still a significant issue.

Preclinical research suggests that radiation-induced cognitive impairment following cranial irradiation is due to the dose received by the neural stem cell (NSC) compartment in the hippocampus dentate gyrus. In a prospective observational study of adult patients with benign or low-grade brain tumours treated with fractionated stereotactic radiation, the authors identified a dosage association between EQD2 to bilateral hippocampi and the chance of long-term memory impairment. An EQD2 to 40% of the bilateral hippocampi (D40%) greater than 7.3 Gy predicts cognitive impairment after 18 months of follow-up [27].

Our study showed outstanding target coverage with good dose homogeneity for the boost volume, achieved 25 Gy coverage to the D98% of whole brain volume, and favourable normal tissue sparing with the HT plan compared with other techniques. The higher hippocampal dose was noted in some patients, possibly due to the boost volume near the hippocampus. The NTCP of the optic structure was low with all the planning proficiencies except optic chiasm.

The current study has certain limitations like the planning system and algorithm used for calculations could also have an impact on the results. The NTCP values in this study were estimated using radiobiological models, which did not consider tumour cell repopulation and oxygenation during the treatment course. Lastly, not all plans used the reference standard Monte Carlo (MC) for calculation.

The techniques like IMRT, VMAT, and HT can reduce the dose received by the hippocampus to the dosimetric threshold in hippocampal avoidance WBRT with a simultaneous boost to selected metastases. The reduction in dosage to the OARs is also possible in all these three planning proficiencies. The planning could be ranked and compared based on the anatomical and clinical challenges of each patient, using dosimetric parameters with the TCP and NTCP estimated radiobiological parameters. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

Statements and Declaration:

Funding : The authors did not receive any funds, grants, or other support during the preparation of this manuscript.

Conflict of interest : The authors declare that they have no conflict of interest with respect to the manuscript.

Ethical Approval : Institutional scientific and Ethics Committee has approved this study. This article does not contain any studies with human participants performed by any of the authors.

Authors Contribution:

The authors confirm contribution to the paper as follows: study conception and design: S. Balasubramanian, M.K. Shobana; Material preparation: S Balasubramanian, C Prekshi, D Anbalagan, P.Thanasekar data collection: S. Balasubramanian, S Joel, D Anbalagan analysis and interpretation of results: S. Balasubramanian; D Anbalagan draft manuscript preparation: S. Balasubramanian, M.K. Shobana. All authors reviewed the results and approved the final version of the manuscript.

Acknowledgements:

The author would like to thank Mr Deepak Arora and Mr George Leo Ranjit, Medical Physicists of Max Super Speciality Hospital, Patparganj, Delhi for their helpful discussion and advice.

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Dosimetric and radiobiological comparison of IMRT, VMAT, and Helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases

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