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Alex Murray

DOS 711 Research Methods in Med Dos I

Case Study Outline
March 12, 2017

Pulsed Reduced Dose Rate (PRDR) for Recurrent Glioma

I. History of Present Illness

a. Patient, AJ, is a 25 year old women with recurrent grade 3 anaplastic astrocytoma,
MGMT methylated, IDH1 mutated, 1p/19q not co-deleted
b. August 22, 2016, AJ developed a left hemibody motor seizure that progressed to a
tonic-clonic seizure and was taken to Gundersen Lutheran, in La Crosse, WI
c. September 14, 2016, MRI showed an ill-defined enhancement and increased T2
FLAIR signal seen throughout the right frontal lobe with increased diffusion
restriction in cerebral blood at the superior and posterior right insular resection
cavity margins
d. 2 subsequent seizures since August, 2016
e. October 18, 2016, biopsy of the T2 enhancing mass found to be consistent with a
grade 3 anaplastic astrocytoma
f. Continued headaches, but have not worsened significantly over the last 6 months
g. Increased heaviness and clonus on left side
h. Increased foot drop, a deficit incurred after her first surgery
i. No new changes in vision or balance
j. Progressive paresthesias mostly in left side fingertips
k. Karnofsky performance score of 90
l. Referred for consultation with radiation oncologist in November, 2016 to discuss
logistics of radiation therapy as a treatment option due to surgery not being a
feasible treatment option.
m. Decided to proceed with radiation therapy treatments
II. Past Medical History
a. Grade 2 astrocytoma, diagnosed August, 2008, maximum safe subtotal resection
completed on August 27, 2008
b. Grade 3 astrocytoma, progression diagnosed November 2010 and right pterional
craniotomy with microsurgical gross total resection of a recurrent operculum,
frontal operculum and insular recurrent astrocytoma performed on January 19,
c. Postoperative adjuvant radiation therapy to 59.4 Gy in 33 fractions, completed on
April 27, 201, received concurrent Avastin
d. History of seizures
e. No history of lupus, scleroderma, or other malignancies

f. Allergic to adhesives, erythromycin, prochlorperazine, penicillin, and silver

g. History of depression
III. Social History
a. Previously enrolled at Western Technical College in La Crosse, WI for medical
administration, withdrew from classes as result of recent illness
b. Moving back in with parents for the duration of radiation treatments
c. Smokes 1 pack of cigarettes a day, counseled on importance of smoking cessation
d. Drinks approximately 1 alcoholic beverage per week
e. Negative pregnancy test prior to start of treatment, counseled on importance of
birth control during or abstinence during radiation treatments
f. Family Medical History
i. Maternal aunt has a benign brain tumor of unknown histology
IV. Medications
a. Acetaminophen, Cyclobenzaprine, Duloxetine, Lamotrigine, Omeprazole,
Oxycodone, Polyethylene glycol., and Senna S., Decadron, Diflucan, Kytril,
Lamictal, Cymbalta, Zofran, Temodar, Bactrim
V. Diagnostic Imaging
a. September 14, 2016 after tonic-clonic seizure MRI showed ill-defined
enhancement and increased T2 FLAIR signal throughout right frontal lobe with
increased diffusion restriction in cerebral blood at the superior and posterior right
insular resection cavity margins and increased T2 FLAIR in right corpus
callosum, cerebral peduncle, midbrain and pons
b. Biopsy on October 18, 2016 of T2 enhancing 2.2x2.2x0.5 cm mass, findings
consistent with grade 3 anaplastic astrocytoma
c. MRI scan on November 2, 2016 with contrast, fused with planning CT scan for
treatment planning
VI. Radiation Oncologist Recommendations
a. Discussed challenges, involvement of brainstem, regarding gross total resection of
b. Surgery not an option, pulsed reduced-dose rate (PRDR) radiotherapy in grade 2
and grade 3 astrocytomas recommended
i. Reirradiation technique developed and used at UW Hospital in Madison,
ii. Reduced dose rate, increased treatment time
iii. Allows sublethal damage repair during irradiation
iv. Palliative benefit
c. The goals of treatment to improve the quantity and quality of life
d. The stage of her progressive tumor means the treatment will not be curative
e. Need for a repeat MRI to better determine the extent of tumor spread
f. Discussed potential acute and long-term side effects of radiation therapy

i. Acute: fatigue, plugging of the ears, otitis media, sore throat, and thrush
ii. Long-term: worsening memory, slowing of cognition, and also potential
VII. The Plan (prescription)
a. Pulse reduced dose rate (PRDR) IMRT
i. 15 fields at 10 different gantry angles
ii. 6 MV for all fields
iii. 3 minutes between fields to deliver radiation at 6.67 cGy/min or 100
MU/min dose rate
iv. Normalized to the 97% isodose line
b. Total dose of 54 Gy given in 27 fractions, 2 Gy per fraction
c. CBCT done prior to every treatment for accurate alignment
VIII. Patient Setup/Immobilization
a. CT simulation done on November 2, 2016 on Siemens Edge 120 kV CT scanner
b. Positioning
i. Head first, supine on 1 inch black mattress with arms down by sides
ii. Head and shoulder board indexed at top of treatment couch
iii. black head dish and custom blue head sponge
iv. Custom Aquaplast mask
v. Large triangle cushion under knees
vi. Velcro strip around patients arms
IX. Anatomical Contouring
a. Fusion of CT simulation scan and MRI completed in MIM 6.4.5 software
b. Contours done in MIM
c. CTV, GTV, PTV, brainstem, optic chiasm, cochleas, and optic nerve contoured by
radiation oncologist
d. Normal structures contoured by dosimetrist and reviewed by radiation oncologist
i. Brain, eyes, lenses, external, skin, spinal cord
e. Constraints for structures given in treatment planning order (TPO)
X. Beam Isocenter/Arrangement
a. Varian TrueBeam radiotherapy system
b. 6 MV for all beams
c. Philips Pinnacle3 used for planning
d. Isocenter autoplaced in PTV volume by dosimetrist
e. Step and shoot IMRT
f. 15 fields
g. Gantry angles
i. 50o, 50o, 90o, 90o, 150o, 180o, 210o, 250o, 250o, 310o, 310o, 315o, 315o, 250o,
h. Couch angles
i. 0o for first 11 fields
ii. 90o for last 4 fields
i. Collimator at 0o for all fields
j. Beam weighting

i. 5%, 5%, 6.4%, 6.4%, 7.4%, 9.4%, 7.1%, 5.9%, 5.9%, 6.7%, 6.7%, 6.2%,
6.2%, 8.9%, 6.8%
k. Field shape created by using 0.7 cm margin around PTV by dosimetrist
XI. Treatment Planning
a. Philips Pinnacle3 used for planning
b. Treatment planning order (TPO) includes prescription and constraints written by
radiation oncologist
c. Dose prescribed to PTV volume using ROI Mean function in Pinnacle
d. Total dose of 54 Gy given in 27 fractions, 2 Gy per fraction
e. Physicist splits beams into certain MUs to accomplish desired dose rate (6.67
cGy/MU or 100 MU/min)
f. 6 MV for all beams
g. Step and shoot IMRT optimized on the PTV volume with a minimum of 4
segments per MU
h. Dose constraints (all met except right cochlea due to close proximity to treatment
i. Brain: Dmax < 60 Gy
ii. Brainstem: Dmax < 64 Gy
iii. Optic Chiasm: Dmax < 54 Gy
iv. Cochlea: Dmean < 35 Gy, Dmax < 40 Gy
v. Lens: Dmax < 7 Gy
vi. Optic Nerve: Dmax < 54 Gy
i. Normalized to 97%
j. Plan evaluated by dosimetrist then radiation oncologist by reviewing DVH and
isodose lines
XII. Quality Assurance/Physics Check
a. MU verification check done with Mobius3D software
i. 5% tolerance
ii. Completed by dosimetrist
b. Delta4+ used for physics QA check
i. 5% tolerance
ii. Completed by physicist
c. Plan passed both QA checks
XIII. Conclusion
a. PRDR feasible treatment option for recurrent gliomas when surgery not an option
b. Biology and physics behind this treatment technique
c. Challenging aspect of plan, length of treatment, patient on table and in mask for
over an hour each treatment
XIV. References
a. Veninga T, Langendijk HA, Slotman BJ, et al. Reirradiation of primary brain
tumours: survival, clinical response and prognostic factors. Radiotherapy and

Oncology. 2001;59(2):127-137.

b. Adkinson J, Tom W, Seo S, et al. Reirradiation of large-volume recurrent glioma
with pulsed reduced-dose-rate radiotherapy. Int J Radiat Oncol Biol Phys. 2011;
79(3): 835-841.