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| ORIGINAL ARTICLES |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 13-20 |
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Step-by-step stereotactic radiotherapy planning of brain metastasis in a surgically resected setting: A guide to radiation oncologists: Dr Kanhu’s ROSE case [Radiation Oncology from Simulation to Execution]
Kanhu C Patro1, Ajitesh Avinash2, Arya Pradhan2, Suresh Tatineni3, Chittaranjan Kundu1, Partha S Bhattacharyya1, Venkata K. R. Pilaka1, Mrityunjaya M Rao1, Arunachalam C Prabu4, Ayyalasomayajula A Kumar4, Srinu Aketi4, Parasa Prasad4, Venkata N. P. Damodara1, Veera S. P. K. Avidi1, Mohanapriya Atchaiyalingam1, Keerthiga Karthikeyan1
1 Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam, Andhra Pradesh, India
2 Department of Radiation Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, Odisha, India
3 Department of Neurosurgery, Medicover Hospital, Visakhapatnam, Andhra Pradesh, India
4 Department of Medical Physics, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam, Andhra Pradesh, India
| Date of Submission | 18-Dec-2021 |
| Date of Decision | 26-Mar-2022 |
| Date of Acceptance | 10-May-2022 |
| Date of Web Publication | 02-Sep-2022 |
Correspondence Address:
Dr. Kanhu C Patro
Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jco.jco_45_21
Background: Surgical resection of brain metastasis is followed by adjuvant radiation in order to reduce the risk of local recurrence. Traditionally, adjuvant radiation was practiced in the form of whole brain radiation therapy that was associated with adverse neurocognitive outcomes and poor quality of life of the patients. In the recent times, stereotactic radiosurgery (SRS) is being practiced as the standard of care for treating brain metastasis cavity with good local control and improved the patient’s quality of life by sparing the normal tissues of adverse effects of radiation. Here, we describe procedure details for stereotactic planning of surgically resected brain metastasis. Materials and Methods: The step-by-step procedure for stereotactic planning of brain metastasis cavity has been described using a clinical scenario of brain metastasis. Results: The stereotactic radiation planning of brain metastasis cavity starts with the basic history and relevant evaluation of symptoms. Magnetic resonance imaging (MRI) of the brain is the imaging modality of choice. The radiation planning of brain metastasis cavity starts with computed tomography (CT) simulation and MRI of brain that should be done in a prescribed format to achieve uniformity in radiation planning. After CT and MRI image fusion, contouring of target, organs at risk (OAR), and radiation planning should be done. The plan evaluation includes target and OAR coverage index, conformity, homogeneity and gradient index, and beam arrangement. After radiation plan evaluation, treatment is delivered after quality assurance and dry run. Conclusion: The paper highlights the sequential process of radiation planning for SRT of brain metastasis cavity, starting from simulation, planning, evaluation of plan, and treatment. Keywords: Brain metastasis, cavity SRS, plan evaluation, radiotherapy planning
How to cite this article:
Patro KC, Avinash A, Pradhan A, Tatineni S, Kundu C, Bhattacharyya PS, Pilaka VK, Rao MM, Prabu AC, Kumar AA, Aketi S, Prasad P, Damodara VN, Avidi VS, Atchaiyalingam M, Karthikeyan K. Step-by-step stereotactic radiotherapy planning of brain metastasis in a surgically resected setting: A guide to radiation oncologists: Dr Kanhu’s ROSE case [Radiation Oncology from Simulation to Execution]. J Curr Oncol 2022;5:13-20 |
How to cite this URL:
Patro KC, Avinash A, Pradhan A, Tatineni S, Kundu C, Bhattacharyya PS, Pilaka VK, Rao MM, Prabu AC, Kumar AA, Aketi S, Prasad P, Damodara VN, Avidi VS, Atchaiyalingam M, Karthikeyan K. Step-by-step stereotactic radiotherapy planning of brain metastasis in a surgically resected setting: A guide to radiation oncologists: Dr Kanhu’s ROSE case [Radiation Oncology from Simulation to Execution]. J Curr Oncol [serial online] 2022 [cited 2023 Nov 30];5:13-20. Available from: http://www.https://journalofcurrentoncology.org//text.asp?2022/5/1/13/355587 |
| Introduction | |  |
The management of brain metastasis has evolved from the traditional whole brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) with time. Following surgical resection of brain metastasis, adjuvant treatment in the form of WBRT or SRS is advocated in order to decrease the risk of local recurrence. Various randomized trials have proved that WBRT is effective in higher local control at post-operative tumor bed as well as distant recurrence in the brain, but it was associated with increased deterioration of patients’ cognition and quality of life. Recent publications and guidelines advocate SRS as the standard of care for limited brain metastasis when compared with WBRT because of similar local control with advantage of higher patients’ cognition and quality of life.[1]
| Material and Methods | | |
Here, the various steps of radiation planning for SRS have been illustrated in an easy way for the beginners using a case of post-operative cavity in a patient with brain metastasis.
| Results | | |
Case History
A 40-year non-smoker male with ECOG 1 had an episode of seizure in the month of March 2020 for a duration of 3–4 min, followed by aura. The seizure was not associated with headache and vomiting. There was no history of involuntary urination or defecation. It was followed by another episode in the month of June 2020 for 2–3 min duration, followed by aura. Post-ictal confusion lasted for 25–30 min. This was also not associated with headache, vomiting, involuntary urination, or defecation.
| Imaging | | |
Contrast-enhanced magnetic resonance imaging (CE-MRI) of the brain showed a well-defined lesion of size 3.2 cm × 3.2 cm in the left occipital and inferior temporal lobe that was hypointense on T1 and brilliantly heterogeneous on T2-weighted image associated with perilesional edema [Figure 1](A). Magnetic resonance spectroscopy showed increased choline and decreased N-acetyl aspartate. With these imaging findings, a preliminary diagnosis of ganglioglioma was made. | Figure 1: Pre-operative magnetic resonance imaging (MRI) of brain showing lesion of size 3.2 cm × 3.2 cm in the left temporo-occipital region (A), post-operative MRI of brain showing post-surgical defect of size 3.2 cm × 3 cm in the left temporo-occipital region (B), and positron emission tomography-computed tomography (PET-CT) scan showing lesion in the upper lobe of right lung of size 2.6 cm × 2.1 cm (C)
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| Surgery | | |
The patient underwent left parieto-occipital craniotomy with gross total excision. The excised tumor was vascular and there was a clear plane of cleavage.
| Histopathology | | |
On post-operative histopathological examination, the tumor was confirmed to be of size 4 cm × 3.5 cm × 1.5 cm and was suggestive of metastatic papillary adenocarcinoma. On immunohistochemistry study, CK 7 and TTF 1 were positive.
| Post-operative Imaging | | |
CE-MRI of the brain revealed a post-surgical defect of size 3.2 cm × 3 cm in the left temporo-occipital region. The cavity was thick-walled having minimal irregular outline. The lesion was hypointense on T1 and hyperintense on T2-weighted image [Figure 1](B).
Whole body positron emission tomography-computed tomography (PET-CT) scan showed a surgical defect in the left parieto-occipital region of the brain measuring size 3.2 cm × 2.4 cm. There was a spiculated lesion in the upper lobe of the right lung of size 2.6 cm × 2.1 cm (SUV max. 3.5). There was also a right paratracheal lymph node of size 1.1 × 1.6 cm (SUV max. 3), and multiple hypermetabolic lymph nodes were seen in the right paratracheal and subcarinal regions [Figure 1](C). With these above findings, a final diagnosis of the carcinoma right lung with brain metastasis (c T4N2M1b) was made.
| Tumor Board Decision on Further Line of Treatment | | |
The patient details were discussed among neurosurgeon, radiation oncologist, and medical oncologist in the tumor board, and stereotactic radiotherapy followed by chemotherapy was decided by the board as the treatment plan.
| Discussion With the Patient | | |
The patient was explained about the procedure, regarding imaging and follow-up, tumor response, the need of radiotherapy (in the form of whole brain radiotherapy/SRS) in the future, and post radiotherapy-raised intracranial tension. He was also explained regarding the tumor control, appearance of new lesions in the future, and the possibility of radionecrosis.
| Pattern of Recurrence | | |
Following surgical resection of brain metastasis, recurrence of leptomeningeal disease (LMD) is seen in about 30% of the cases. There are basically two types of recurrence, i.e., classic LMD and nodular LMD. LMD develops due to hematogenous spread, direct spread of the disease, or tumor spillage to cerebrospinal fluid during surgery.[2]
| Dose Selection | | |
Currently, single fraction SRS (12–20 Gy in 1 fraction) is advocated as the standard of care for adjuvant therapy for post-operative cavity, but it requires dose reduction for tumors larger than 3 cm for radiation-induced safety. The tumor with size >3 cm requires coverage of the areas of affected meninges and part of craniotomy, thereby increasing the volume to be encompassed within the target volume, thus increasing more tissue at risk of radiation necrosis. The use of fractionated SRS (27 Gy in 3 fractions or 30 Gy in 5 fractions) gives the liberty of coverage of such larger volumes and delivery of dose with higher biologically effective dose than single fraction SRS while maintaining safety. In multiple studies, it was seen that local tumor bed control was better with fractionated SRS when compared with single fraction SRS.[1]
| Decision by the Radiation Tumor Board | | |
As the tumor size was >3 cm and in order to include the larger volume of adjacent dura and craniotomy tract, fractionated SRS was planned by the Radiation Tumor Board to a marginal dose of 30 Gy in 5 fractions at 5 Gy/fraction.
| Radiation Planning | | |
Here we describe the steps of treatment of brain metastasis post-operative cavity by stereotactic radiotherapy from simulation to plan execution.
| Time Interval Between Surgery and Start of Radiation | | |
Alghamdi et al.[3] in their paper have reported that there was greater shrinkage of post-operative cavity in larger tumors, i.e., >3 cm and in early post-operative period (<21 days) as this may lead to irradiating more normal tissues. Thus, radiation should begin not less than 21–28 days following surgery.
| Step 1: CT simulation | | |
During simulation, the patient was set up in the supine position with neutral neck position and immobilization was done using the FRAXION thermoplastic mask and stereotactic frame [Figure 2](A). Fiducials were placed on the thermoplastic mask after proper alignment with the lasers. Intravenous contrast was given at a dose of 1 mL per kg body weight. Then, CT scan was taken from the vertex to neck with CT slice thickness of 1 mm, as depicted in [Table 1] and [Figure 2](B). After simulation, the DICOM CT images were sent to our Oncentra server which was then imported for delineation of target and organ at risk (OAR). The CT scan of this patient was done on the post-operative 28th day of surgery, keeping in mind the cavity remodeling. | Figure 2: Immobilization of the patient using the stereotactic thermoplastic mask and frame during CT simulation (A), CT scan taken during CT simulation (B), and fusion of MRI of the patient with planning CT scan (C)
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 | Table 1: CT simulation and MRI protocol to be followed for brain metastasis cavity SRS
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| Step 2: MRI protocol | | |
MRI brain of the patient was done using 512 × 512 matrix in the neutral neck position similar to that of CT scan during simulation with no gap, no tilt, and 1 mm slice thickness, as depicted in [Table 1]. The field of view included the body contour along with nose, eyes, and skull. The MRI included the usual T1, T2, FLAIR sequences. In addition, the 3D FSPGR was used to view the normal anatomy.
| Step 3: Image fusion | | |
These acquired MRI sequences were fused with the planning CT scan by contouring the eyes, lens, basilar artery, sinuses, and calcification, and matching was done using the auto-fusion technique to help in target and OAR delineation [Figure 2](C).
| Step 4: Target delineation | | |
The target delineation was performed as per the consensus contouring guidelines for post-operative completely resected cavity SRS for brain metastasis.[4] As this was a post-operative setting, there was no gross tumor volume (GTV). The clinical target volume (CTV) included the entire contrast-enhancing surgical cavity seen in the gadolinium-enhanced T1-weighted MRI scan excluding the edema. The CTV included a 5 mm margin along the bone flap beyond the initial region of pre-operative tumor contact as the tumor was in contact with the dura in the pre-operative MRI scan. If the tumor was not in contact with the dura, then CTV should include a margin of 1–5 mm along the bone flap. CTV included a margin of 1–5 mm along the sinus as the tumor was in contact with a venous sinus in the pre-operative MRI scan.
Here, we propose a simple mnemonic “ABCDE” that can be used while target delineation was performed for the post-operative cavity SRS, where A = adjacent dura to lesion and surgical tract, B = bone flap inner part, C = cavity proper, D = dural sinus, E = enhancing component on CE-MRI.
Thus, the total CTV: A + B + C + D + E [Figure 3](A)]-(F). | Figure 3: Clinical target volume (CTV) delineation showing delineation of adjacent dura (A), bony flap (B), surgical cavity (C), dural sinus (D), contrast-enhanced region (E), and total CTV (F)
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The planning target volume (PTV) was drawn taking 1 mm around the CTV [Figure 4](A). Smoothing of the contour was done from the adjacent bone. Multi-planar evaluation, i.e., evaluation of both the GTV and PTV, was done in all the three planes: axial, coronal, and sagittal [Figure 4](B)]-(D). | Figure 4: Delineation of planning target volume (PTV) (A), evaluation of CTV and PTV in axial view (B), coronal view (C), and sagittal view (D)
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In the present case, the CTV volume was 4.65 cc and the PTV volume was 37.491 cc.
| Step 5: OAR delineation | | |
The OAR delineation included the cochlea, brainstem, optic chiasma, and optic apparatus. The cochlea was contoured in the bone window setting, whereas other OARs, i.e., brainstem, optic chiasma, and optic apparatus, were contoured using the MRI that was fused with the planning CT. Also brain CTV was also drawn as an OAR [Figure 5](A). | Figure 5: Delineation of organs at risk (A), isodose lines: 100% (dark green), 80% (light green), 60% (light blue), 50% (pink), 40% (dark blue) (B), and cone beam computed tomography correction of patient during treatment (C)
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| Step 6: Radiation technique | | |
Radiation planning can be done using any of the RT techniques such as intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT), dynamic conformal arc therapy (DCARC), or three-dimensional conformal radiotherapy (3DCRT), according to the convenience of the radiation physicist and physician.
In the present case, planning was done using the VMAT technique.
| Step 7: Plan evaluation | | |
After the completion of planning by the physicist, the evaluation for treatment plan was done using the following indices as noted below:
PTV coverage index
Following planning, the coverage of the PTV needs to be seen. The prescription isodose level was such that not 100% of the prescribed dose covered 100% of the PTV. Often, 95% of the prescription dose covered 95% or higher percentage of the PTV, and otherwise 100% of the prescription dose covered 95% or higher percentage of the PTV.[5]
In the present case, 95% of the prescription dose covered 99.9% of the PTV and 100% of the prescription dose covered 99.15% of the PTV, which satisfied the aforementioned parameter for the PTV coverage as depicted in [Table 2]. | Table 2: Various indices of plan evaluation of brain metastasis cavity SRS in the current case
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| Intracranial organ at risk index | | |
Keeping in mind the desirable dose constraints to the OAR, we need to check the dose to individual OARs.[6]
The dose desirable and dose achieved for all the OARs in the present case are depicted in [Table 3]. | Table 3: Organs at risk with their desirable dose and dose achieved in the current case
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| Whole brain minus CTV dose | | |
As per Faruqi et al.,[7] in order to reduce the risk of adverse effects following fractionated SRS, the volume of brain minus CTV receiving 30 Gy dose should be limited to 10.5 cc.
In the current case, the 30 Gy volume of brain–CTV was 10.30 cc.
| Conformity index | | |
To note the conformity index of the SRS, here we used two types of conformity indices, i.e., the RTOG conformity index and the Paddick conformity index.[5],[8]
The RTOG conformity index (CIRTOG) was calculated using the following formula:
CIRTOG = Volume of prescription isodose/PTV volume.
In this case, the RTOG conformity index was 1.17 [Table 2].
Paddick conformity index (CIPaddick) was calculated using the following formula:
CIPaddick = (Volume of prescription isodose in the area of interest, i.e., PTV)2/PTV volume × Volume of prescription isodose.
Here in the current case, the Paddick conformity index was 0.96 [Table 2].
| Homogeneity index | | |
It is calculated using the following formula:
Homogeneity index = Maximum dose/Prescription dose.
In this case, the homogeneity index was 1.21 [Table 2].
| Dose fall off | | |
The dose fall off observation is very much needed in the plan evaluation under the heading of gradient index. For this we need to calculate the difference between various isodose lines. In order to calculate the difference between the isodose lines, we need to calculate the equivalent radius.
| Equivalent radius calculation | | |
To evaluate the dose gradient, we have to find out the difference between the radius of various isodose lines. But none of the isodoses is spherical. So, we use the following formula to calculate the equivalent radius.
1st: Find out the specified isodose volume.
2nd: Calculate the radius of the isodose volume by using the formula:
V = 4/3 π r3,
r = (3V/4 π)1/3.
The calculation of volume and radius of various isodose lines in the present case is shown in [Table 2].
| Gradient Index | | |
The formula for calculating gradient index is as given below.
Gradient index = Equivalent radius of 50% isodose−Equivalent radius of prescription isodose. Ideally, the gradient index should be between 0.3 and 0.9 mm.
In the current case, the gradient index was 2.19−3.15 mm = 0.96 mm, which is close to the ideal gradient index [Table 2].
| Distance between various isodose lines | | |
The various isodose lines are depicted in [Figure 5](B).
The ideal difference between 80% and 60% isodose lines should be <2 mm.[9]
In the current case, it is 0.4 mm.
The ideal difference between 80% and 40% isodose lines should be <8 mm.
In the present case, it is 1 mm.
| Beam arrangement | | |
The arrangement of the beams was done such that there is adequate coverage of the target while giving less dose to the OARs. It should be noted that the beams should not pass through the ipsilateral eye.
| Choosing the appropriate plan | | |
During radiation planning, out of all the plans, three plans were chosen for comparison, as shown in [Table 4]. Plan 3 had the highest V30Gy, D100%, and monitor units (MUs) with lowest (brain—PTV) dose and 50% volume. Thus plan 3 was chosen for treatment which has less integral dose, even though MU is more.
| Step 8: Quality assurance (QA) | | |
Mechanical isocenter check was done using the Winston–Lutz test, and the point dose verification was done keeping the tolerance as 1 mm.[10]
| Step 9: Dry run | | |
Treatment verification consists of setup reproduction, isocenter verification, and clinically verifying each treatment field—check beam clearance, check any interlock—MLC interlock, and potential MU problems. Then the immobilization devices are clearly marked after successful dry run.
| Step 10: Pre-medication protocol | | |
Prior to the start of the treatment, pre-medication was delivered in the form of tablets as described below: all starting the day before start of RT treatment.
Tablet Dexamethasone 8 mg thrice daily
Tablet Ondansetron 8 mg thrice daily
Tablet Pantoprazole 40 mg once daily
If the patient is diabetic, proper diabetic care needs to be taken.
| Step 11: Setup verification and treatment delivery | | |
It includes cone beam CT correction [Figure 5](C). After all the corrections had been done treatment was delivered.
| Step 12: Post-medication | | |
It is an optional protocol that usually includes anti-emetics, proton pump inhibitors, and tapering the dose of steroids over a week. Steroids and anticonvulsants were given to the patient to decrease the chance of edema and seizures during and after treatment.
| Step 13: Advice and follow-up | | |
After the completion of the treatment, the patient was usually advised to follow after 6 months for imaging.
Supplementary file
Here, we also provide the Brain Metastasis SRS Plan Evaluation sheet as a supplementary file that will help in proper and accurate plan evaluation for every post-operative cavity SRS case of brain metastasis.
| Conclusion | | |
This paper conceptualizes and acts as an easy guide for the stereotactic radiotherapy treatment of post-operative cavity brain metastasis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 2. | Roshan SP, Brandon ET, Anthony LA, Samuel RM, John BF, Paul MF, et al. A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases. Neuro-Oncology 2019;21:1049-59. |
| 3. | Alghamdi M, Hasan Y, Ruschin M, Atenafu EG, Myrehaug S, Tseng CL, et al. Stereotactic radiosurgery for resected brain metastasis: Cavity dynamics and factors affecting its evolution. J Radiosurg SBRT 2018;5:191-200. |
| 4. | Soliman H, Ruschin M, Angelov L, Brown PD, Chiang VLS, Kirkpatrick JP, et al. Consensus contouring guidelines for postoperative completely resected cavity stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2018;100:436-42. |
| 5. | Metcalfe P, Liney GP, Holloway L, Walker A, Barton M, Delaney GP, et al. The potential for an enhanced role for MRI in radiation-therapy treatment planning. Technol Cancer Res Treat 2013;12:429-46. |
| 6. | Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, et al. UK consensus on normal tissue dose constraints for stereotactic radiotherapy. Clin Oncol (R Coll Radiol) 2018;30:5-14. |
| 7. | Faruqi S, Ruschin M, Soliman H, Myrehaug S, Zeng KL, Husain Z, et al. Adverse radiation effect after hypofractionated stereotactic radiosurgery in 5 daily fractions for surgical cavities and intact brain metastases. Int J Radiat Oncol Biol Phys 2020;106: 772-9. |
| 8. | Petkovska S, Tolevska C, Kraleva S, Petreska, E Conformity index for brain cancer patients. Proceedings of the Second Conference on Medical Physics and Biomedical Engineering of R Macedonia. Macedonia: The Former Yugoslav Republic of Association for Medical Physics and Biomedical Engineering of R Macedonia, Vol. 43, 2010. p. 111. |
| 9. | Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 2011;29:134-41. |
| 10. | Denton TR, Shields LB, Howe JN, Spalding AC Quantifying isocenter measurements to establish clinically meaningful thresholds. J Appl Clin Med Phys 2015;16:5183. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]
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