Clinical trial NCT01508221
Conditions: Brain Metastasis
Keywords: brain metastasis
Sponsor: University of Cincinnati
Start date: 2011-06-01; Completion date: 2017-02-01
Enrollment: 31 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine whether the use of Trental and Vitamin E can help reduce the incidence of radiation necrosis (a lesion that usually occurs at the original tumor site) after radiosurgery. These two drugs are commonly used to treat radiation necrosis when it occurs but the hope is that these drugs can be used to prevent radiation necrosis from ever occurring.

Detailed description:
The treatment phase of the study is 6 months. Study procedures will be conducted such as: history, physical and neurological exam, pregnancy testing (for women of child bearing age) and a Brain MRI. Follow-up appointments will be every 3 months for 1 year at which time, your participation in the study will be concluded.

Arms: arm 1: Trental 400 mg TID and Vitamin E 400IU BID starting the first day after the last radiosurgery treatment
Interventions: intervention 1: Trental intervention 2: Vitamin E
Intervention descriptions: intervention 1: 400 mg tid starting first day after last radiosurgery treatment and continuing for 6 months intervention 2: 400IU twice daily starting the first day after last radiosurgery treatment and continuing for 6 months

Protocol documents:
Prot_SAP_000.pdf: 
A PHASE II TRIAL TO EVALUATE THE USE OF TRENTAL AND VITAMIN E 
FOR PROPHYLAXIS OF RADIATION NECROSIS  
 
 
Investigators: 
 
Neurosurgery  
Ronald E. Warnick M.D. 
nsgymd@me.com  
513-475-8629 
 
Chris McPherson, M.D. 
cmcpherson@mayfieldclinic.com 
 
Radiation Oncology 
John Breneman M.D.  
John.Breneman@uchealth.com 
 
Lauren Imwalle M.D. 
imwallle@ucmail.uc.edu  
 
Jessica Guarnaschelli, M.D. 
Jess.Guarnaschelli@uchealth.com 
 
Luke Pater, M.D. 
Luke.Pater@uchealth.com 
 
Biostatistics and Epidemiology 
Rakesh Shukla, PhD 
 
Clinical Trial Management 
UC Cancer Institute Clinical Trials Office 
513-584-7698 
 
 
 
 
 
 
 
 
Version 04-25-12 
Amendment 2 
 
 
 
Amendment 2 04/25/12 


 
 
1. Aims 
1.1. The goal of this single arm Phase II study is to evaluate the prophylactic use of 
Trental and vitamin E for its efficacy in reducing radiation necrosis after 
radiosurgery. 
 
2. Background and Significance 
2.1. Hypothesis: 
2.1.1. Vitamin E and Trental are commonly used in combination to treat cerebral 
radiation necrosis after radiosurgery.  Use of these drugs after radiosurgery 
may serve as prophylaxis for and reduce the incidence of radiation necrosis. 
2.2. Background: 
2.2.1. Radiation Necrosis Review:   
2.2.1.1. 
Radiosurgery is widely used in the treatment of various intracranial 
disorders such as metastatic brain tumors, meningiomas and 
arteriovenous malformations (1-3).  However, the use of radiosurgery is 
limited by the risk of injury to adjacent brain.  Although technological 
advances have considerably enhanced the safety and efficacy of 
radiosurgery, radiation necrosis continues to be a serious complication 
of treatment.  A recent study at our institution showed that 14% of 
metastatic lesions treated with radiosurgery exhibited imaging 
characteristics consistent with radiation necrosis (4).  Several other 
studies have confirmed this observation and have shown that 
radiographic changes can be present in up to 46% (5-7).  Typically, 
radiation injury is categorized into acute, subacute and chronic stages 
based upon the time between radiation treatment and onset of 
symptoms (8).  Imaging characteristics are variable and can range from 
T2 FLAIR abnormalities to areas of contrast enhancement and frank 
necrosis.  Clinical symptoms can be associated with these radiographic 
changes and can range from mild headaches to progressive neurologic 
deterioration.  Steroids are a commonly used form of treatment for 
radiation induced injury.  However, patients who progress despite 
steroid treatment are often candidates for oral therapy with Trental and 
vitamin E.  This combination has been widely used to treat radiation 
induced injury and will often reverse both clinical and radiographic 
effects (9-16).  A recent randomized controlled trial showed that this 
combination is effective in the treatment of superficial radiation 
induced fibrosis over the chest, in patients receiving radiotherapy for 
breast cancer (13).  Also, a recent study suggested that the combination 
may be effective in the treatment of radiation induced brain injury (14). 
The goal of this study is to determine whether this commonly used 
treatment for radiation necrosis can be used prophylactically to prevent, 
delay and/or reduce the severity of cerebral radiation necrosis after 
radiosurgery. 
 
 
 
 
 
 
 
 
 
 
  
Amendment 2 04/25/12 


3. Investigator Experience 
3.1. Dr. Warnick is a board-certified neurosurgeon who has undergone fellowship 
training in neurosurgical-oncology at the University of San Francisco.  He has 
published extensively in the field of neurosurgical oncology and currently has an 
academic neurosurgical practice with an active oncology component.  He has 
also had extensive experience in the diagnosis and treatment of central nervous 
system radiation necrosis.   
3.2. Dr. Breneman is a board-certified radiation oncologist.  He has published 
extensively in the field of radiation oncology and currently has an academic 
radiation oncology practice.  He has also had extensive experience in the 
diagnosis and treatment of central nervous system radiation necrosis.   
 
4. Experimental Design and Methods 
4.1. Patient Registration: 
4.1.1. Only patients who meet eligibility requirements may be registered. 
4.1.2. Once an eligible patient is identified by the treating physician, informed 
consent for participation in the study is obtained.  
4.1.3. A baseline evaluation form and enrollment form (See Appendix B) is 
completed. 
4.2. Pretreatment Evaluation: 
4.2.1. Prior to initiation of treatment, a complete history and physical with a 
detailed neurologic examination is required.   
4.2.2. Evaluation of further metastatic disease may be performed as clinically 
indicated.  
4.3. Treatment Phase: 
4.3.1. Patients will receive a combination of Trental 400 mg TID and Vitamin E 
400IU BID starting the first day after the last radiosurgery treatment.  This 
regimen is then continued on a daily basis for a period of 6 months after the 
last radiosurgery treatment. 
4.3.2. Patients will be monitored with regular clinic visits and MRIs performed 
at 3 month intervals.  A follow up form (Appendix B) will be filled out by 
the treating physician at each visit. 
4.3.3. All patients will be followed for an appropriate duration as clinically 
indicated.  
4.3.4. Enrolled patients that require additional radiosurgery will discontinue 
Trental and Vitamin E for the two weeks prior to the additional radiosurgery 
and resume treatment the day after.  These patients will remain on study, but 
the new site disease will not be followed in the necrosis analysis. 
4.4. Data Analysis and Monitoring 
4.4.1. Study Endpoints: 
4.4.1.1. 
Primary 
4.4.1.1.1. 
Incidence of symptomatic radiation necrosis 
4.4.1.1.2. 
Incidence of asymptomatic radiation necrosis 
4.4.1.2. 
Secondary 
4.4.1.2.1. 
Change in volume of contrast enhancement  
4.4.1.2.2. 
Change in volume of necrosis 
Amendment 2 04/25/12 


4.4.1.2.3. 
Change in volume of T2 edema 
4.4.1.2.4. 
Steroid usage 
4.4.2. Results of the Data analyses will be  reported over all as well as by 
stratifying with respect to: 
4.4.2.1. 
Radiation prescription dose 
4.4.2.2. 
Lesion volume 
4.4.2.3. 
Presence of comorbidities: Hypertension, Diabetes 
4.4.3. As per the design, at the first stage we would evaluate the results by 
identifying when we have 8 lesions with necrosis. If at that stage, we have 
52 or more lesions in the study then that would confirm we should continue 
to complete the study with all 134 lesions. At that stage, if we find 14 or less 
lesions with radiation necrosis, we would then claim that the study has met 
its objective of a 50% reduction in incidence of radiation necrosis (from 15% 
to 7.5%).  (see Appendix A) 
4.4.4. Summary of Data Submission (See Appendix B) 
4.4.4.1. 
Enrollment Form (EF) 
 
Within 2 wks of registration 
4.4.4.2. 
Initial Evaluation Form (IF)     
Within 2 wks of registration  
4.4.4.3. 
Treatment Form (TF)  
 
At the end of radiosurgery 
4.4.4.4. 
Follow Up Form (FF)  
 
Every 3 months for 1 year 
4.4.4.5. 
Follow MRI Form (MF) 
 
Every 3 months for 1 year 
4.4.5. Treatment Form (TF) will be completed by treating physician. 
4.4.6. MRI documentation 
4.4.6.1. 
The contrast-enhanced MRI performed pre-radiosurgery and every 
3 months post-radiosurgery will be evaluated by the investigators: 
REW, JB, LI.  Form MF will be completed by investigator LI. 
4.4.6.2. 
Radiation necrosis will be defined as previously reported by 
Blonigen et al. (4): 
A combination of criteria will be used including appearance 
on serial MRI scans, MR Spectroscopy and histology 
(when available).  It will be further described as the 
following: (1) patient with radiographic changes with a 
requirement of steroid therapy, (2) 2 consecutive scans with 
persistent MRI changes consistent with radiation necrosis, 
(3) findings suggestive of radiation necrosis on MR 
Spectroscopy, or (4) histological evidence of radiation 
necrosis. 
4.4.6.3. 
Once radiation necrosis is identified by the treating physician, 
parameters will be quantified using standard radiation oncology 
software tools by an investigator: LI.  The volume of contrast 
enhancement, T2 edema and necrosis will be quantified. 
4.5. Data storage and confidentiality 
4.5.1. Data will be maintained in a password protected database  and will only be 
accessed by the listed investigators.    The information gathered will not be 
used or disclosed for any other purpose other than this specific research 
project. 
 
Amendment 2 04/25/12 


5. Estimated period of time to complete the study. 
5.1. It is estimated that the patient recruitment period will be 2 years and the follow 
up period will be one year.  Total estimated time to complete the study is 3 years.   
 
6. Human Subjects:  Describe the characteristics of the research population: 
6.1. Subjects will include patients receiving or planning to undergo single fraction or 
five fraction radiosurgery for a metastatic brain tumor.   
6.2. The demographics of the study population are expected to reflect the general 
population with intracranial metastatic tumors.  Only adults > 18 years of age 
will be included in the study. 
6.3. Recruitment: 
6.3.1. Patients seen at the University of Cincinnati Brain Tumor Center will be 
directly recruited by the treating physician.   
6.4. This study is estimated to require 49 patients.  In a recently published study 
performed at the University of Cincinnati (4), patients recruited to the study had 
an average of 2.75 metastatic lesions.  Each lesion was treated independently 
when analyzing the incidence of radiation necrosis.  Using this same method, a 
total of 134 lesions are necessary to show a 50% effective reduction in radiation 
necrosis with our supplement.   This would be estimated to require 49 patients.   
6.5. Inclusion Criteria: 
6.5.1. Patients about to undergo or currently receiving single or five fraction 
radiosurgery for a metastatic brain tumor. 
6.5.2. Diagnosis of a metastatic brain tumor may be accomplished by histologic 
confirmation or by clinical confirmation by the treating physician based on 
MR Imaging characteristics in the setting of a known history of cancer. 
6.5.3. Availability for follow up  
6.5.4. Ability to give informed consent.  
6.5.5. Age > 18 years 
6.5.6. Patients who have had partial or total resection of a metastatic tumor are 
eligible. 
6.6. Exclusion Criteria: 
6.6.1. Known sensitivity to vitamin E or Trental  
6.6.2. Pregnant or nursing women.  
6.6.3. Recent intracranial bleed or retinal hemorrhage 
6.6.4. Major medical or psychiatric illness which in the investigators opinion 
will prevent administration or completion of the protocol therapy and/or 
interfere with followup. 
6.6.5. Treatment with a non-approved or investigational drug within 30 days 
before day 1 of study treatment.   
 
6.6.6. History of Avastin treatment. 
6.6.7. Anticipated need for treatment with Avastin. 
6.6.8. Patients currently on vitamin E or Trental are ineligible. 
6.6.9. History of bleeding disorder 
6.6.10. Patient who is on Warfarin, Lovenox, NSAIDS, or aspirin.  Low dose (81 
mg) of daily aspirin is acceptable. 
Amendment 2 04/25/12 


6.6.11. History of liver disorder 
6.6.12.  Intolerance to methylxanthines such as caffeine, theophylline, and 
theobromine. 
 
 
7. Risk/Benefit Assessment. 
7.1. The combination of vitamin E and Trental is a commonly used treatment for 
radiation induced injury to the brain as well as other body organs (9-14).  
7.2. Vitamin E (α-tocopherol):   
7.2.1. It is thought that the therapeutic benefits in combating radiation induced 
injury are due to its antioxidant properties and its inhibition of TGF-β and 
collagen production (15,16).  As a common component in over the counter 
multivitamins, the toxicity profile of vitamin E is low and the dosage of 400 
IU BID used for the study presents minimal risk to the patient.   
7.3. Trental (Pentoxyfilline):  
7.3.1. Several mechanisms of action have been proposed for the potential 
benefits of Trental in radiation induced injury.  However, the exact 
mechanism is unclear.  Trental may decrease the inflammatory response and 
formation of oxygen radicals (2,9).  The dosage of Trental used in this study 
is typically well tolerated and presents minimal risk to the patient.  Common 
side effects of Trental include gastrointestinal effects such as nausea, 
vomiting, dyspepsia; nervous system effects such as headache, dizziness, 
insomnia and cardiovascular effects such as palpitations, flushing and 
angina.  While typically minor, side effects have necessitated 
discontinuation of Trental in approximately 3% of treated patients.   
7.4. The benefits of this study include the possibility of providing a prophylactic 
regimen for the prevention of radiation necrosis.    
 
8. Payment 
8.1. None 
 
9. Subject Costs: 
9.1. All tests and procedures involved in this study are considered standard of care 
and would be the responsibility of the patient and/or  insurance.    Vitamin E is 
available over the counter and trental is available by prescription. 
 
 
11. Literature Cited  
1. Petrovich Z, Yu C, Giannotta SL, et al. Survival and pattern of failure in brain 
metastases treated with stereotactic Gamma Knife radiosurgery. J Neurosurg 
2002;97:499–506 
 
Amendment 2 04/25/12 


2. Lutterbach J, Cyron D, Henne K, et al. Radiosurgery followed by planned 
observation in patients with one to three brain metastases. Neurosurgery 
2003;52:1066–1074. 
 
3. Mehta MP, Tsao MN, Whelan TJ, et al. The ASTRO evidence based review of the 
role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2005;63:37–
46. 
4. Blonigen, B.J., Steinmetz, R.D., Levin, L., Lamba, M.A., Warnick R.E., Breneman, 
J.C.,  Irradiated volume as a predictor of brain radionecrosis after linear accelerator 
stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2009 Sep 22 (Epub ahead of 
print) 
5. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain 
radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases. 
JAMA 2006;295: 2483–2491. 
 
6. Sneed PK, Lamborn KR, Forstner JM, et al. Radiosurgery for brain metastases: Is 
whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys 1999;43:549–558. 
 
7. Voges J, Treuer H, Sturm V, et al. Risk analysis of linear accelerator radiosurgery. Int 
J Radiat Oncol Biol Phys 1996;36:1055–1063 
 
8. Warnick R. E., Darakchiev, B. J., Breneman, J.C., Stereotactic radiosurgery for 
patients with solid brain metastases: current status.  J Neuro-onc 2004; 69: 125-137. 
9. Chiao, T. and Lee, A., Role of Pentoxyfilline and vitamin E in attenuation of 
radiation induced fibrosis.  Annals of Pharmacotherapy 2005; 39:516-522. 
10. Delanian S. Striking regression of radiation-induced fibrosis by a combination of 
pentoxifylline and tocopherol. Br J Radiol 1998;71:892- 4. 
 
11. Fischer M, Wohlrab J, et al., Crux medicorum ulcerated radiation-induced fibrosis—
successful therapy with pentoxifylline and vitamin E. Eur J Dermatol 2001;11:38- 
40. 
12. Sezen, O., Ertekin, M. V., et al., Vitamin E and L-carnitine, separately or in 
combination in the prevention of radiation-induced brain and retinal damages.  
Neurosurg Rev 2008; 31:205-213.   
13. Delanian S, Porcher R, et al.  Randomized, Placebo-Controlled Trial of Combined 
Pentoxifylline and Tocopherol for Regression of Superficial Radiation-Induced 
Fibrosis.  J Clin Oncol 2003;21:2545-2550. 
Amendment 2 04/25/12 


14. Williamson R, Kondziolka D, et al.  Adverse Radiation Effects after Radiosurgery 
May Benefit from Oral Vitamin E and Pentoxifylline Therapy: A Pilot Study.  
Stereotact Funct Neurosurg 2008;86:359-366. 
15. O’Sullivan B and Levin W. Late radiation-related fibrosis; pathogenesis, 
manifestations, and current management. Semin Radiat Oncol 2003;13: 274-89. 
 
16. Lefaix J.L., Delanian S., et al., Striking regression of subcutaneous fibrosis induced 
by high doses of gamma rays using a combination of pentoxifylline and alpha-
tocopherol: an experimental study. Int J Radiat Oncol Biol Phys 1999;43:839- 47. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amendment 2 04/25/12 


 
 
 
 
Appendix A 
Two-Stage Clinical Trials Sample Size (Results are in the form of NON-RN as 
success) 
 
TO DETECT  RN REDUCTION FROM 15% ( HISTORICAL) to 10%  
(a 33.3% reduction) 
 
 
Possible Designs For P0=0.850, P1=0.900, Alpha=0.050, Beta=0.200 
 
 
 
 
 
 
 
 
Constraints 
 
N1 
R1 
PET 
N 
R 
Ave N 
Alpha 
Beta 
Satisfied 
 
124 106 
0.598 
288 254 
189.88 
0.047 
0.198 
Optimum 
 
 
In the first stage, we need to see 124 lesions on supplement and if we find 106 or less 
lesions RN-free, the trial stops. If you find 107 or more lesions RN free, the trial 
continues and we go all the way to 288 lesions. If we find 255 or more lesions RN free 
(in other words- 33 or fewer RN), we have proven that the trial succeeded in reducing the 
RN incidence from 15% to 10% by giving them supplement.  
 
TO DETECT  RN REDUCTION FROM 15% ( HISTORICAL) to 7.5%  
(a 50 % reduction) 
 
 
Possible Designs For P0=0.850, P1=0.925, Alpha=0.050, Beta=0.200 
 
 
 
 
 
 
 
 
Constraints 
 
N1 
R1 
PET 
N 
R 
Ave N 
Alpha 
Beta 
Satisfied 
 
 
 
52 
44 
0.528 
134 120 
90.69 
0.047 
0.200Optimum & Minimax 
 
 
 
 
 
FOR A REDUCTION OF RN FROM 15% to 5% (a 66.7% reduction) 
 
Possible Designs for P0=0.85, P1=0.950, Alpha=0.050, Beta=0.200 
 
 
 
 
 
 
 
 
Constraints 
 
N1 
R1 
PET 
N 
R 
Ave N 
Alpha 
Beta 
Satisfied 
 
 
13 
11 
0.602 
65 
59 
33.71 
0.049 
0.200 
Optimum 
 
 
You can interpret similarly as above for a reduction of RN from 15% to 5%.  
 
Amendment 2 04/25/12 


 
References 
Simon, Richard. 'Optimal Two-Stage Designs for Phase II Clinical Trials', Controlled 
Clinical Trials, 1989, 
     Volume 10, pages 1-10. 
 
Report Definitions 
N1 is the sample size in the first stage. 
R1 is the drug rejection number in the first stage. 
PET is the probability of early termination of the study. 
N is the combined sample size of both stages. 
R is the combined drug rejection number after both stages. 
Ave N is the average sample size if this design is repeated many times. 
Alpha is the probability of rejecting that P<=P0 when this is true. 
Beta is the probability of rejecting that P>=P1 when this is true. 
P0 is the response proportion of a poor drug. 
P1 is the response proportion of a good drug. 
 
Summary Statements 
The optimal two-stage design to test the null hypothesis that P<=0.850 versus the 
alternative 
that P>=0.950 has an expected sample size of 33.71 and a probability of early termination 
of 
0.602. If the drug is actually not effective, there is a 0.049 probability of concluding that 
it is (the target for this value was 0.050). If the drug is actually effective, there is a 
0.200 probability of concluding that it is not (the target for this value was 0.200). After 
testing the drug on 13 lesions in the first stage, the trial will be terminated if 11 or fewer 
respond. If the trial goes on to the second stage, a total of 65 lesions will be studied. If 
the total number responding is less than or equal to 59, the drug is rejected. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amendment 2 04/25/12 


 
 
 
 
Appendix B 
 
A PHASE II TRIAL TO EVALUATE THE USE OF TRENTAL AND VITAMIN E 
FOR PROPHYLAXIS OF RADIATION NECROSIS  
 
Enrollment Form 
 
Name:_________________________    DOB:____________   MRN:_____________                
 
Date:___________     
 
Yes 
No 
 
Patient is about to undergo single or five fraction radiosurgery for a 
metastatic   brain tumor. 
 
Able to give informed consent.  
 
Age > 18 years 
 
Patient has no known sensitivity/allergy to vitamin E, Trental, caffeine, 
theophylline, or theobromine. 
 
Patient is not pregnant or nursing. 
 
Patient has not had a recent intracranial bleed or retinal hemorrhage or 
history of a bleeding disorder. 
 
Patient has no major medical or psychiatric illness which in the 
investigators opinion will prevent administration or completion of the 
protocol therapy and/or interfere with followup. 
 
Patient has not had treatment with a non-approved or investigational drug 
within 30 days prior to day 1 of study treatment.   
 
Patient is not a current smoker. 
 
Patient has no history of Avastin treatment. 
 
Patient has no anticipated need for treatment with Avastin. 
 
Patient is not currently on vitamin E or Trental  
Amendment 2 04/25/12 


 
Answer to each of the above questions must be “Yes” in order for patient enrollment 
 
Signature:________________________________ Date: ______________________ 
A PHASE II TRIAL TO EVALUATE THE USE OF TRENTAL AND VITAMIN E 
FOR PROPHYLAXIS OF RADIATION NECROSIS  
 
Initial Evaluation Form 
 
Name:_____________              DOB:____________ 
MRN:_________________ 
Date:___________     
 
 
Location: 
 
 
Size 
 
 
 
_____________________ 
_____________ 
 
_____________________ 
_____________ 
_____________________ 
_____________ 
_____________________ 
_____________ 
                 
 
HPI:___________________________________________________________________
________________________________________________________________________ 
________________________________________________________________________
________________________________________________________________________
______________________________ 
 
ROS : 
Headaches 
Visual Changes      Hearing Changes      Sensory Changes 
 
 
Seizure 
Memory loss        Weakness                  Cognitive Changes 
 
Other:______________________________________________________ 
 
PMH:    
Diabetes 
Hypertension    Prior Radiotherapy   Other:____________ 
PSH:  __________________________________________________________________ 
 
KPS: _________   
 
 
 
 
 
ECOG: __________ 
 
EXAM:    Mental Status       Normal               ___________________________________ 
    
     Language              Normal               ___________________________________ 
 
     CN 2-12                Normal              ___________________________________ 
 
     Motor                    Normal              ___________________________________ 
  
     Sensation               Normal       
  ___________________________________ 
 
     Reflexes                Normal              ___________________________________ 
 
Medications:     Dexamethasone  dose:   _________________ 
  
 
    Anticonvulsant:_________     
 
 
    Aspirin dose: ___________ 
 
 
    NSAIDS daily dose: ____________ 
Amendment 2 04/25/12 


 
 
     Anticoagulants: _________________ 
                       Other Meds:   ____________________________________________  
 
Signature:________________________________ Date: ______________________ 
 
 
 
A PHASE II TRIAL TO EVALUATE THE USE OF TRENTAL AND 
VITAMIN E FOR PROPHYLAXIS OF RADIATION NECROSIS  
 
Follow Up Form 
 
Name:_____________    DOB:____________   MRN:_____________
 
Date:___________     
 
 
Radiation Necrosis Evaluation: Defined as 1) patient with radiographic changes with a 
requirement of steroid therapy, 2) 2 consecutive scans with persistent MRI changes 
consistent with radiation necrosis, 3) findings suggestive of radiation necrosis on MR 
Spectroscopy, or 4) histological evidence of radiation necrosis. 
Location: 
 
 
 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
_____________________ 
  Radiation Necrosis                  Sx             ASx 
 
S:______________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________  
 
ROS : 
Headaches 
Visual Changes      Hearing Changes      Sensory Changes 
 
 
Seizure 
Memory loss        Weakness                  Cognitive Changes 
 
      Other:______________________________________________________ 
 
Trental SE:  GI Upset 
Headache        Dizziness    Other:_____________________ 
Vitamin E SE:    Blurred Vision      Bruising      Skin Changes   Other: ______________ 
 
KPS: _________   
 
 
 
 
 
ECOG: __________ 
 
EXAM:    Mental Status       Normal               ___________________________________ 
    
     Language              Normal               ___________________________________ 
 
     CN 2-12                Normal              ___________________________________ 
 
     Motor                    Normal              ___________________________________ 
  
     Sensation               Normal       
  ___________________________________ 
 
     Reflexes                Normal              ___________________________________ 
Amendment 2 04/25/12 


 
Medications:     Dexamethasone dose:   _________________ 
 
 
    Keppra dose:_________       Dilantin dose:  ___________       
    Other Anticonvulsant dose:_____________________________  
 
 
 
    Compliant with Trental and Vitamin E 
 
 
                             Aspirin dose: ___________ 
 
 
     NSAIDS daily dose: ____________ 
 
 
     Anticoagulants: _________________ 
Other Meds:   ____________________________________________                        
_________________________________________________________ 
 
Disease Status: 
 
 
Response              yes                 no 
 
 
Necrosis               yes                  no 
                        Recurrence           yes                 no 
 
Overall Clinical Picture: ___________________________________________________ 
_______________________________________________________________________ 
 
Signature:________________________________ Date: ______________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amendment 2 04/25/12