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Group 3
Clinical Practicum III
Craniospinal Irradiation Project
November 9, 2016

Proton Craniospinal Irradiation


Introduction
Compared to x-ray radiation therapy for Craniospinal Irradiation (CSI), proton therapy is
more effective in delivering dose to the target and sparing the normal tissues due to the
characteristics of Bragg-peak and hence the absence of exiting dose from proton beams.1
Because exit dose is absent in proton beam therapy, there is significantly less integral dose
compared with photon therapy techniques. New pencil beam scanning (PBS), also known as spot
scanning, is able to deliver intensity-modulated proton therapy (IMPT), which can further reduce
the dose to normal tissue and minimize secondary neutron contamination and deliver the dose to
the target more precisely at the same time.2 The IMPT is considered a superior technique for
pediatric patients over other proton therapy techniques. In addition, the newly developed robust
optimization method of IMPT allows multi-field optimization for large targets without field
junction shifting, which is an advantage for CSI planning.3 Thus, for this CSI project, the
technique of PBS proton therapy was used to deliver the IMPT plan to the patient.
Target and OR's delineation
The patient was simulated in supine position for comfort and easier access for
anesthesia.4 The clinical target volumes (CTV) contained the entire brain and the spinal canal
including the thecal sac. Optical nerves were included in the CTV as suggested in a recent study
of CSI proton therapy.5 Cribriform plate was also included in the CTV to ensure adequate
coverage, as studies show that underdose of the cribriform plate region caused relapse of
medulloblastoma in the subfrontal brain area.6
In conventional CSI treatment, multiple fields have to be accurately matched by doing
collimator rotation angle and gap calculations. To minimize over and under dose to the spinal
cord, a weekly shift of field junctions has to be performed. To reduce the complexity of manual

feathering and take advantage of inverse planning, IMRT, volumetric modulated arc
radiotherapy (VMAT), and IMPT have been used for CSI. Usually, several small regions are
contoured at the junction area and different dose levels were set for inverse optimization to
simulate a gradient region at the junction. The concept of robust optimization has recently been
implemented in commercial treatment planning software, like RayStation, to take the worst case
scenario into consideration during optimization. Generally CTV is used as the target for
optimization and a robust optimization is performed to account all the uncertainties caused by
proton range, setup, and anatomical motion.2, 7 The idea of this project is to use robust
optimization to optimize the dose in the junction area without creating any extra contours. In a
CSI proton plan, 4 to 5 fields are used. When robust optimization is used for independent beams,
as shown in Figure 1, the total number of scenarios is too much for the optimizer to compute. So
in this IMPT planning, only the superiorinferior direction robust optimization was used to
compensate the over and under dose of the matching fields.7 To compensate the setup errors and
anatomical motions in the other directions, a pencil beam scattering target volume (PBSTV) was
generated by adding a 3 mm margin to the anterior and posterior directions of the brain CTV,
and the left and right directions of spinal CTV, and a 1 mm margin to the left and right directions
of the brain CTV and the anterior and posterior directions of the spinal CTV, which were also the
beam directions. Since robust optimization was used for the superior and inferior directions to
compensate the field misalignment uncertainties at the field junctions, no margin was added in
these two directions. All organs at risk (OR) shown in Table 2 were contoured. The PBSTV and
OR are shown in Figure 2 and 3.

Figure 1. Robust optimization settings for CSI IMPT planning. A 0.3 cm uncertainty in Sup-Inf
direction was used. Independent beams were checked to account all possible combinations of
patient ISO shift uncertainties.

PBSTV
Optic
nerves

Figure 2. Brain PBSTV (blue) includes the optic nerves (green)

PBSTV

CTV

Figure 3. Spinal PBSTV (blue) and CTV (green)

Treatment planning process


The couch angle was at 0 degree. For the brain PBSTV, two parallel opposed lateral
beams that share the same iso-center were added. Since the maximum field size is 21 cm of our
proton machine, three posterior beams were placed to cover the whole spinal portion of the
PBSTV. The cranial beams overlapped with the superior spinal beams by a few centimeters, and
each two adjacent spinal beams overlapped with each other as well. Each spine field has its own
iso-center. All iso-centers were at the same level and same lateral couch position to minimize
shifts. The beam arrangement and iso-centers are shown in Figure 4.

Figure 4. Beam arrangement and iso-centers

A dose of 36 Gy at 1.8 Gy per day was prescribed to the target volume. A 3mm setup
uncertainty in the superior-inferior direction and 3.5% range uncertainty for the PBSTV were

used for robust optimization (Figure 1). IMPT is delivered by scanning the target volume layerby-layer. By switching energies the proton beams penetrate the target volume at different depths
so that the Bragg peaks stop at different layers. A 1 cm wall with 1 mm gap outside the PBSTV
was generated to keep the dose more conformal. The plan optimization objectives are shown in
Figure 5.

Figure 5. Plan optimization objectives

Plan evaluation and discussions


The coverage of the PBSTV was successfully achieved. 95.1% of the PTV received the
prescribed dose. The maximum dose, defined as the dose to 1% of the PTV6, was 108% of the
prescription dose. Table 1 shows the dosimetry parameters for the target volume. Figure 6 shows
the iso-dose distribution. Figures 7 and 8 show the DVH for the OR and PBSTV. The dose
constraints for all the OR were all met. (Table 2)

Table 1. Dosimetry parameters for the target volume


Target Parameters

Desired Objective

Achieved objective

Maximum Plan Dose (D1):

< 5% of PTV to receive 3960 cGy

3888 cGy

D99:

> 3240 cGy

3359 cGy

V100:

> 95%

95.1%

V95:

> 34.2 Gy (or 95%)

98.9%

Figure 6. Iso-dose distribution

Figure 7. Plan DVH for the OR

Figure 8. Plan DVH for the pencil-beam scatter target volume

Table 2. Desired and achieved objectives for each organ at risk


Organ at risk

Desired

Achieved

Constraints

Objective(s)

Objective(s)

Met/Exceeded

Heart

Mean < 320 cGy

6 cGy

Met

Stomach

V22.5 < 10 cc

0 cc

Met

Lung rt

Mean < 700 cGy

80 cGy

Met

Lung lt

Mean < 700 cGy

107 cGy

Met

Liver

Mean < 1800 cGy

4 cGy

Met

Kidney rt

Mean < 1500 cGy

6 cGy

Met

Kidney lt

Mean < 1500 Gy

7 cGy

Met

Bowel

V24 < 20 cc

0 cc

Met

Rectum

V27.5 < 20 cc

0 cc

Met

Bladder

V16.8 < 15 cc

0 cc

Met

Femur rt

V24 < 10 cc

0 cc

Met

Femur lt

V24 < 10 cc

0 cc

Met

Mandible

DMax < 3600 cGy

800 cGy

Met

Parotids

Mean < 2600 cGy

274 cGy

Met

Submandibular Glands

Mean < 2600 Gy

57 cGy

Met

Glottis

Mean < 2600 Gy

24 cGy

Met

Thyroid

V45 < 100%

0.0

Met

Lens

DMax < 700 cGy

105 cGy

Met

This technique takes into consideration of the field misalignment uncertainties and
optimizes to generate a decreasing dose gradient in the overlapped junction area of one field, and
an increasing dose gradient in the same area of the adjacent field. Figure 9 shows the dose
gradient in the cranial fields and the mid-spinal field when the superior spinal field is removed.
By adding a line dose profile in that area as shown in Figure 10, the dose gradient, as displayed

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in Figure 11, can be measured. Thus, the proton CSI plan is able to achieve field junction
homogeneity and substantially reduce dose to healthy tissues.

Dose gradient

Dose gradient

Figure 9. Dose gradient in the overlapped field junctions

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Line dose profile

Figure 10. The line dose profile added to measure the dose gradient (orange)

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Figure 11. The dose gradient of the overlapped area for the two adjacent fields

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The hot spots locate at the superior part of the cranial PTV, due to the reduced thickness
of anatomy. The cold spots are at the junction area between fields, which are caused by robust
optimization to prevent hot spots when adjacent fields overlap more than predefined.
For both conventional and IMPT techniques, the higher sensitivity to organ motion was
thought to be the biggest disadvantage to proton therapy, as the beams are not synchronized with
organ motion during beam delivery.8 The newly developed robust optimization method of IMPT
has been demonstrated to account for the range and patient setup uncertainties including tumor
shrinkage, patient weight gain/loss, field misalignment, intrafractional organ motion, etc.2 In
recent published research, the plan robustness was evaluated for robust optimized and
conventional non-robust IMPT plans by shifting the isocenter 3 mm per field.3 Results showed
the deviation for the simulated mismatching error was significantly smaller than that in the
conventional plan, which proved the robust optimization is able to compensate the setup errors
for multi-isocenter fields. This robust optimization method of IMPT allows multi-field
optimization for large targets without field junction shifting, which is an advantage for CSI
planning.
Proton therapy, especially PBS therapy, has been proven to be effective and superior
when treating the craniospinal axis compared to standard photon therapy. The aforementioned
benefits surrounding PBS proton therapy supports the superiority of proton therapy. However,
proton therapy presents with disadvantages of which includes monetary constraints on facilities
to support such equipment and patients to receive treatments of that caliber. Proton therapy
equipment also requires a large operating space within the facility or another spare building. For
the robust optimization, too many scenarios will significantly increase the optimization time. As
a result, more experience is still needed in balancing the number of scenarios and plans adequate
robustness. Lastly, since proton therapy is a newer technique, quality assurance programs are
limited and facilities must implement their own programs until national protocols become
available.8

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Conclusion
The IMPT using robust optimization is able to account iso shift uncertainties in CSI
treatments. The planning process is much simpler and more robust than other methods. The
doses to the OR and normal tissues are considerably less than photon treatments, which is critical
for young patients.

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References
1. Liu H, Chang JY. Proton therapy in clinical practice. Chin J Cancer. 2011;30(5):315-326.
http://dx.doi.org/10.5732/cjc.010.10529
2. Liu W, Zhang X, Li Y, Mohan R. Robust optimization of intensity modulated proton therapy.
Med Phys. 2012;39(2):1079-1091. http://dx.doi.org/10.1118/1.3679340
3. Liao L, Lim GJ, Li Y, et al. Robust optimization for intensity modulated proton therapy
plans with multi-Isocenter large fields. Int J Part Ther. September 2016.
http://dx.doi.org/10.14338/IJPT-16-00012.1
4. South, M. Using Composite Planning and Delivery with Feathered Junctions in
Craniospinal, Brain-Spine and Spine-Spine Abutted Fields. [PowerPoint]. Methodist Cancer
Center; 2015.
5. Lin H, Ding X, Kirk M, et al. Supine craniospinal irradiation using a proton pencil beam
scanning technique without match line changes for field junctions. Int J Radiat Oncol Biol
Phys. 2014;90(1):71-78. http://dx.doi.org/10.1016/j.ijrobp.2014.05.029
6. Paulino AC. Radiotherapeutic management of medulloblastoma. Oncology (Williston Park).
1997;11(6):813-823, 827-828, 831.
7. Liu W, Frank SJ, Li X, et al. PTV-based IMPT optimization incorporating planning risk
volumes vs robust optimization. Med Phys. 2013;40(2):021709-1-8.
http://dx.doi.org/10.1118/1.4774363
8. Khan FM, Gibbons JP. The Physics of Radiation Therapy. 5th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2014.