nrg-cc001
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nrg-cc001
appendix i

| Non-small-cell and small-cell lung cancer                                                                                             | GPA Scoring Criteria   | Patient         |           |       |     |       |
|---------------------------------------------------------------------------------------------------------------------------------------|------------------------|-----------------|-----------|-------|-----|-------|
| Prognostic Factor                                                                                                                     | 0                      | 0.5             | 1.0       | Score |     |       |
| Age, years                                                                                                                            | > 60                   | 50-60           | < 50      |       |     |       |
| KPS                                                                                                                                   | < 70                   | 70-80           | 90-100    |       |     |       |
| EM                                                                                                                                    | Present                | Absent          |           |       |     |       |
| No. of BM                                                                                                                             | > 3                    | 2-3             | 1         |       |     |       |
| Sum total                                                                                                                             |                        |                 |           |       |     |       |
| Median survival (months) by GPA: 0-1.0 = 3.0; 1.5-2.0 = 5.5; 2.5-3.0 = 9.4; 3.5-4.0 = 14.8                                            |                        |                 |           |       |     |       |
| Melanoma                                                                                                                              | GPA Scoring Criteria   | Patient         |           |       |     |       |
| Prognostic Factor                                                                                                                     | 0                      | 1.0             | 2.0       | Score |     |       |
| KPS                                                                                                                                   | < 70                   | 70-80           | 90-100    |       |     |       |
| No. of BM                                                                                                                             | > 3                    | 2-3             | 1         |       |     |       |
| Sum total                                                                                                                             |                        |                 |           |       |     |       |
| Median survival (months) by GPA: 0-1.0 = 3.4; 1.5-2.0 = 4.7; 2.5-3.0 = 8.8; 3.5-4.0 = 13.2                                            |                        |                 |           |       |     |       |
| Breast cancer                                                                                                                         | GPA Scoring Criteria   | Patient         |           |       |     |       |
| Prognostic Factor                                                                                                                     | o                      | 0.5             | 1.0       | 1.5   | 2.0 | Score |
| KPS                                                                                                                                   | 55                     | 60 70-80 90-100 | n/a       |       |     |       |
| Subtype                                                                                                                               | Basal                  | n/a   LumA      | HER2 LumB |       |     |       |
| Age, years                                                                                                                            | ≥ 60                   | < 60            | n/a       | n/a   | n/a |       |
| Sum total                                                                                                                             |                        |                 |           |       |     |       |
| Median survival (months) by GPA: 0-1.0 = 3.4; 1.5-2.0 = 7.7; 2.5-3.0 = 15.1; 3.5-4.0 = 25.3                                           |                        |                 |           |       |     |       |
| Renal cell carcinoma                                                                                                                  | GPA Scoring Criteria   | Patient         |           |       |     |       |
| Prognostic Factor                                                                                                                     | Score                  |                 |           |       |     |       |
| O                                                                                                                                     | 1.0                    | 2.0             |           |       |     |       |
| KPS                                                                                                                                   | < 70                   | 70-80           | 90-100    |       |     |       |
| No. of BM                                                                                                                             | > 3                    | 2-3             |           |       |     |       |
| Sum total                                                                                                                             |                        |                 |           |       |     |       |
| Median survival (months) by GPA: 0-1.0 = 3.3; 1.5-2.0 = 7.3; 2.5-3.0 = 11.3; 3.5-4.0 = 14.8                                           |                        |                 |           |       |     |       |
| GI cancers                                                                                                                            | GPA Scoring Criteria   | Patient         |           |       |     |       |
| Prognostic Factor                                                                                                                     | Score                  |                 |           |       |     |       |
| KPS                                                                                                                                   | < 70                   | 70              | 90        | 100   |     |       |
| 80                                                                                                                                    |                        |                 |           |       |     |       |
| Median survival (months) by GPA: 0-1.0 = 3.1; 2.0 = 4.4; 3.0 = 6.9; 4.0 = 13.5                                                        |                        |                 |           |       |     |       |
| Sperduto PW, Kased N, Roberge D, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-         |                        |                 |           |       |     |       |
| specific tool to estimate survival for patients with brain metastases. Journal of clinical oncology: official journal of the American |                        |                 |           |       |     |       |
nrg-cc001
diagnosis-specific graded prognostic assessment (ds-gpa)

specific tool to estimate survival for patients with brain metastases. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2012;30(4):419-425.  
Graded Prognostic Assessment (GPA) worksheet to estimate survival from brain metastases (BM) by diagnosis. Subtype: Basal: triple negative; LumA: ER/PR positive, HER2 negative; LumB: triple positive; HER2: ER/PR negative, HER2 positive. ECM, extracranial metastases; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; KPS, Karnofsky performance score; LumA, luminal A;
LumB, luminal B; PR, progesterone receptor.
appendix ii (24aug2017) certification and
step 1 - examiner certification

Institutions with patients participating in the quality of life/neurocognitive function components of this study must meet certification requirements for administering neurocognitive assessments. The healthcare professional (e.g., nurse, psychologist) who is responsible for test administration in this study must be pre-certified by Dr. Wefel (See Section 8.3). Examiners who have completed the full certification procedure to perform these tests for RTOG 0825, 0834, 1114, NRG-BN001 or NRG-CC003 during the past 6 months do not need to complete the full certification procedure again, but the certification worksheet for NRG-CC001 must be faxed to Dr. Wefel for documentation purposes with information regarding the examiners prior certification (protocol number, date of certification). If these criteria are met, each examiner and NRG will be notified of the examiner's recertification status for NRG-CC001. Examiners who have not completed the full certification procedure for RTOG 0825, 0834, 1114, NRG-BN001 or NRGCC003 within the past 6 months must complete the full certification procedure to be recertified to ensure continued familiarity with study procedures. All certified test administrators are required to attest to their proficiency in the language (English or French) in which the test is administered to the patient. Only certified test administrators proficient in the primary language of the patient are permitted to test the patient. Prior to registering and/or testing a patient, potential examiners must:
1) Read the protocol 2) Read this Appendix (Certification and Administration Procedures for the Neurocognitive Test Battery)
3) Go to the NRG Oncology web site and use your username and password to access the link entitled, "Neurocognitive Training Procedure Letter" on the CC001 forms section of the NRG Oncology website. This letter will provide you with the web address and study specific password for the training video.  
4) Obtain copies of the Neurocognitive Function Test packets (containing the HVLT-R,
TMT and COWA), and the NRG-CC001 Blank Forms, pages 46-49 (containing the Neurocognitive Function Coversheet), and the Training Video Post Test from the NRG Oncology website 5) Watch the training video 6) Complete the Training Video Post Test 7) Complete a "practice" assessment with the Neurocognitive Function Test packet 8) Complete the Certification Worksheet (Appendix I) 9) All materials (i.e., Training Video Post Test, completed practice assessment and Neurocognitive Function Coversheet, certification worksheet) must be scanned and emailed (NeuropsychologyResearch@mdanderson.org) or faxed (713-794-4999) to Dr. Wefel, who will review it and correct any procedural errors with the trainee.  
10) If the trainee demonstrates competency, he/she will be notified of the certification approval to administer the tests to study subjects as part of NRG-CC001. A certification  
NRG-CC001 1 - Version Date: September 26, 2017
approval notice will be sent to NRG for the registration process and to ensure that only NRG-CC001-approved examiners are testing subjects on protocol NRG-CC001.  
11) All neurocognitive materials for every patient at every time point must be uploaded to Medidata Rave® within 7 days after test administration.
appendix ii (24aug2017) certification and
step 2 - neurocognitive test

Two of the tests to be administered have alternate forms or versions in order to reduce the effects of practice. The tests have been grouped together in Packets that contain alternate versions of these neuropsychological tests. Please administer the tests in the order prescribed in the test packets. To ensure that the correct order is maintained per patient, please ensure that the NCF test packets are used in the order provided. If for any reason neurocognitive testing was not performed at an applicable patient visit, please use the next sequential packet at the next applicable visit (ie Patient Visit 1 = Packet 1, Patient Visit 2 = neurocognitive testing missed, Patient Visit 3 = Packet 2).  
| Pre-Treatment                                                                                  | Month 2**   | Month 4**   | Month 6**   | Month 12**   |          |
|------------------------------------------------------------------------------------------------|-------------|-------------|-------------|--------------|----------|
| Assessment                                                                                     |             |             |             |              |          |
| NCF Packet                                                                                     | Packet 1    | Packet 2    | Packet 3    | Packet 4     | Packet 5 |
| Label **Neurocognitive testing should be performed as close to the day of the MRI as possible. |             |             |             |              |          |
appendix ii (24aug2017) certification and
step 3 - test instructions

1. Testing must be completed in one session. Test instructions must be followed verbatim with every patient at every study visit. All tests should be completed in black pen.  
2. Tests should be administered in the following order to every patient and at every study visit:
HVLT-R Part A (Trials 1-3); Trail Making Test Part A; Trail Making Test Part B; COWA; HVLT-R Part B (Delayed Recall); and the HVLT-R Part C (Delayed Recognition).  
3. You may fill the delay interval between COWA and HVLT-R Part B (Delayed Recall) with QOL questionnaires.  
4. Follow the instructions on the Forms Packet Index before submission of forms to NRG. 5. All neurocognitive materials for every patient at every time point must be uploaded to Medidata Rave® within 7 days after test administration. Please keep all original test forms. In the event of questions, contact Dr. Wefel. Results remain on file at the institution as source documentation pending request for submission by NRG or a study chair.  
6. All test results are recorded on the Neurocognitive Function Coversheet, which is found in the Forms Packet. Study/case-specific labels must be applied to all forms.  
7. Patients should not be given copies of their tests to avoid learning the material between test administrations.  
8. Before dismissing the patient, thank the patient for his/her participation. 9. In the event that a patient cannot complete a given test, please write the reason(s) on the test form AND the Neurocognitive Function Coversheet.
appendix ii (24aug2017) certification and
1. hopkins verbal learning test-revised

Part A - Free Recall: Complete the three learning trials first Part B - Delayed Recall: Complete after a 20 minute delay that includes administration of Trail Making Tests and COWA as well as the symptom self-report measures if appropriate Part C - Delayed Recognition: Complete immediately after Delayed Recall
appendix ii (24aug2017) certification and
2. trail making test [timed

Part A - Sample: The Sample for Part A must be completed/attempted by each patient and every assessment. Place the Sample A worksheet flat on the table, directly in front of the patient (the bottom of the worksheet should be approximately six inches from the edge of the table). Give the patient a black pen and say: Examiner*: "On this page* (point) *are some numbers. Begin at number 1* (point to 1) *and draw* a line from 1 to 2 (point to 2), *2 to 3* (point to 3)*, 3 to 4* (point to 4), *and so on, in order, until* you reach the end (point to the circle marked END). *Draw the lines as fast as you can.* Ready, begin." If the patient completes Sample A correctly and in a manner demonstrating that s/he understands what to do, proceed immediately to Test A. If the patient makes a mistake on Sample A, point out the error and explain it. The following explanations of mistakes serve as illustrations:
- *"This is where you start (point to number 1)"*
- *"You skipped this circle (point to the circle omitted)"*
- "You should *go from number 1 to 2, 2 to 3, and so on, until you reach the circle marked* END"
If it is clear that the patient intended to touch a circle but missed it, do not count it as an omission. Remind the patient, however, to be sure to touch the circles. If the patient still cannot complete Sample A, take his/her hand and guide him/her through the trail using the opposite end of the pen, lightly touching the worksheet to avoid making marks on the copy. Then say: Examiner*: "Remember, begin at number 1 (*point to 1*) and draw a line from 1 to 2 (*point to 2*), 2 to 3 (*point to 3*), 3 to 4 (*point to 4*) and so on, in order, until you reach the circle marked* END (point). Do not skip around, but go from one number to the next in proper order. Remember to work as fast as you can. Ready, begin." If the patient does not succeed, or it becomes evident that s/he cannot do the task, DISCONTINUE testing and indicate the corresponding reason on the Trail Making Test Data Sheet and the Neurocognitive Function Coversheet. If the patient completes Sample A correctly and appears to understand what to do, proceed immediately to Part A.  
Part A - Test: After the patient has completed Sample A, place the Part A test worksheet directly in front of the patient and say: Examiner*: "Good! Let's try the next one. On this page are numbers from 1 to 25. Do this the* same way. Begin at number 1 (point*) and draw a line from 1 to 2 (*point to 2*), 2 to 3 (*point to 3*), 3 to 4 (*point to 4*) and so on, in order, until you reach the circle marked END (*point). Do not skip around, but go from one number to the next in proper order. Remember to work as fast as you can. Ready, begin."
- Start timing as soon as the instruction is given to "begin" - Watch closely in order to catch any errors as soon as they are made. If the patient makes an error, call it to his/her attention immediately and have him/her proceed from the point the mistake occurred NRG-CC001 4 - Version Date: September 26, 2017  
- The patient must complete the test in 3 minutes or less
- DO NOT STOP TIMING UNTIL HE/SHE REACHES THE CIRCLE MARKED "END"
- If the patient does not complete the test within 3 minutes terminate the testing. The test can also be discontinued if the patient is extremely confused and is unable to perform the task. Collect the worksheet and complete the Trail Making Data Sheet and the Neurocognitive Function Coversheet indicating the reason the test was terminated and the last correct number reached on the test.  
- If the patient successfully completes the test collect the worksheet and record the time to completion on the Trail Making Test Data Sheet and the Neurocognitive Function Coversheet in minutes and seconds. Then say, "*That's fine. Now we'll try another one."*
Part B - **Sample:** The Sample for Part B must be completed/attempted by each patient and every assessment. Place the Sample B worksheet flat on the table, directly in front of the patient (the bottom of the worksheet should be approximately six inches from the edge of the table) and say: Examiner*: "On this page (*point*) are some numbers and letters. Begin at number 1 (*point to 1*) and draw a line from 1 to A (*point*), A to 2 (*point to 2*), 2 to B (*point to B*), B to 3 (***point to** 3*), 3 to C (*point to C*) and so on, in order, until you reach the end (*point to the circle marked END*). Remember, first you have a number (*point to 1*), then a letter (*point to A*), then a number* (point to 2), then a letter (point to B), and so on. Draw the lines as fast as you can. Ready, begin."  
If the patient completes Sample B correctly, and in a manner demonstrating that s/he understands what to do, proceed immediately to Part B. If the patient makes a mistake on Sample B, point out the error and explain it. The following explanations of mistakes serve as illustrations:
- *"You started with the wrong circle. This is where you start (point to number 1)"*
- *"You skipped this circle (point to the circle omitted)"*
- *"You should go from number 1 (*point*) to A (*point*), A to 2 (*point to 2*), 2 to B (***point to**
B*), B to 3 (*point to 3*) and so on, until you reach the circle marked END (***point**)"
If it is clear the patient intended to touch a circle but missed it, do not count it as an omission. Remind the patient, however, to be sure to touch the circles. If the patient still cannot complete Sample B, take their hand and guide them through the trail using the opposite end of the pen, lightly touching the worksheet to avoid making marks on the copy. Then say: Examiner*: "Now you try it. Remember, begin at number 1 (*point to 1) and draw a line from 1 to A (point to A*), A to 2 (*point to 2*), 2 to B (*point to B*), B to 3 (*point to 3*) and so on, in* order, until you reach the circle marked END (point*). Ready, begin."* If the patient does not succeed or it becomes evident that s/he cannot do the task, DISCONTINUE testing and indicate the corresponding reason on the Trail Making Test Data Sheet and the Neurocognitive Function Coversheet. If the patient completes Sample A correctly and appears to understand what to do, proceed immediately to Part A.
appendix ii (24aug2017) certification and
part b - test

After the patient has completed Sample B, place the Part B Worksheet directly in front of the patient and say: Examiner: " Good! Let's try the next one. On this page are both numbers and letters. Do this the same way. Begin at number 1 (point*) and draw a line from 1 to A (*point to A), A to 2 (point to 2*), 2 to B (*point to B*), B to 3 (*point to 3*), 3 to C (*point to C*) and so on, in order,* until you reach the circle marked END (point*). Remember, first you have a number (*point to 1*), then a letter (*point to A), *then a number (*point to 2*), then a letter (*point to B), and so on. Do not skip around, but go from one circle to the next in the proper order. Draw the lines as fast as you can. Ready, begin."
- Start timing as soon as the instruction is given to "begin"
- Watch closely in order to catch any errors as soon as they are made. If the patient makes an error, call it to his/her attention immediately and have him/her proceed from the point the mistake occurred - do NOT start from the beginning
- The patient must complete the test in 5 minutes or less - DO NOT STOP TIMING UNTIL HE/SHE REACHES THE CIRCLE MARKED "END" - Collect the worksheet and record the time to completion on the Trail Making Test Data Sheet in minutes and seconds
- If the patient does not complete the test within 5 minutes terminate the testing. The test can also be discontinued if the patient is extremely confused and is unable to perform the task. Collect the worksheet and complete the Trail Making Test Data Sheet and the Neurocognitive Function Coversheet indicating the reason the test was terminated and the last correct number or letter reached on the test.  
- At the top of both Sample forms and both Test forms please write: patient initials, NRG
case number, date of evaluation, institution name, name of certified tester, and the certified tester's phone number.
appendix iii
3. controlled oral word association

| Class I   | 1.                                                                                                                                                         | KPS ≥ 70,   |
|-----------|------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| 2.        | Primary controlled,                                                                                                                                        |             |
| 3.        | Age < 65,                                                                                                                                                  |             |
| 4.        | Metastasis in brain only                                                                                                                                   |             |
| Class II  | KPS ≥ 70 and 1 of the following: - Primary uncontrolled - Primary controlled, age ≥ 65 - Primary controlled, age < 65,  metastases in brain & other  sites |             |