September After Valid...1.92% 1 0.00% 0 1.92% 1 1.92% 1 0.00% 0 TOTAL 52 # OTHER (PLEASE SPECIFY)...

75.00% 39

9.62% 5

15.38% 8

0.00% 0

1.92% 1

5.77% 3

0.00% 0

7.69% 4

Q1 What is your occupation/role? (select all that apply)Answered: 52 Skipped: 0

Total Respondents: 52

# OTHER (PLEASE SPECIFY) DATE

1 Laboratory Geneticist 9/12/2019 8:11 AM

2 Laboratory Scientific Director 9/12/2019 7:07 AM

3 Bioinformatician 9/12/2019 5:08 AM

4 Clinical Fellow 9/9/2019 12:09 PM

Pathologist

Physician(non-patholo...

MedicalDirector

Technologist/Technician

QA/QCCoordinator

LaboratoryManager

Industry

Other (pleasespecify)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

ANSWER CHOICES RESPONSES

Pathologist

Physician (non-pathologist)

Medical Director

Technologist/Technician

QA/QC Coordinator

Laboratory Manager

Industry

Other (please specify)

1 / 36

CAP Diffuse Gliomas: DRAFT Recommendations and Strength of Recommendations

DisclaimerThe information, data, and draft recommendations provided by the College of American Pathologists are presented for informational and public feedback purposes only.The draft recommendations and supporting documents will be removed on October 7, 2019.The draft recommendations along with the public comments received and completed evidence review will be reassessed by the expert panel in order to formulate the final recommendations. These draft materials should not be stored, adapted, or redistributed in any manner.

Not Vali

d Afte

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tembe

r 30,

2019

78.85% 41

7.69% 4

1.92% 1

3.85% 2

0.00% 0

0.00% 0

1.92% 1

Q2 Which of the following best describes your practice setting? (selectone)

Answered: 52 Skipped: 0

Universityhospital/aca...

Voluntary,non-profit...

Proprietaryhospital

City/County/State hospital

Veteranshospital

Army/AirForce/Navy...

National/corporate laboratory

Regional/localindependent...

Public Health,non-hospital

Clinic, group,or doctor...

Industry orvendor


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


University hospital/academic medical center

Voluntary, non-profit hospital

Proprietary hospital

City/County/State hospital

Veterans hospital

Army/Air Force/Navy hospital

National/corporate laboratory

2 / 36


Not Vali

d Afte

r Sep

tembe

r 30,

2019

1.92% 1

0.00% 0

1.92% 1

1.92% 1

0.00% 0

TOTAL 52


There are no responses.

Regional/local independent laboratory (except clinic or group practice and not owned by a national corporation(s))

Public Health, non-hospital

Clinic, group, or doctor office laboratory

Industry or vendor


3 / 36



Not Vali

d Afte

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65.63% 21

25.00% 8

9.38% 3

Q3 Draft Recommendation Statement 1IDH mutational testing must beperformed on all DGs in the appropriate clinical and pathologic setting.

(Quality of Evidence: Moderate; Strength of Recommendation:Strong)Please note: The “appropriate clinical and pathologic setting” will

be described in greater detail in the manuscript.Answered: 32 Skipped: 20

TOTAL 32

# COMMENTS DATE

1 The WHO blue book suggestion that over age of 55 IDH1 immunostaing is sufficient seemsreasonable to me and should be incorporated

9/11/2019 10:27 PM

2 IDH mutational testing must be performed on all DGs unless they are midline and show a H3K27Mmutation.

9/11/2019 10:10 AM

3 As a general rule, I believe it best to use “should” for a strong recommendation and “may” for aconditional recommendation. Guidelines are suggestions/recommendations — they have no force.As such, “must” doesn’t seem appropriate. None of the above is intended to weaken therecommendation or change the authors recommendation

9/11/2019 8:06 AM

4 Why not consider IDH1 IHC as a possible solution especially in labs that do. It have moleculartechnology to do mutation assays?

9/10/2019 1:33 PM

5 not diagnostic, occurs in all grades 9/10/2019 11:58 AM

6 IDH mutational testing should also be done on all cases suspected of being diffusely infiltrativegliomas.

9/10/2019 8:56 AM

7 specify sequencing vs IHC 9/10/2019 4:02 AM

8 If IDH1 immuno is positive, mutation analysis is not necessary 9/9/2019 10:22 PM

9 No financial support and manpower shortage 9/9/2019 3:47 PM

Agree aswritten

Agree withsuggested...

Disagree(please incl...

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


Agree as written

Agree with suggested modifications (please include comments)

Disagree (please include comments)

4 / 36


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10 Agree, just want to emphasize it would be great to provide guidance on when IHC based (R132H)testing is sufficient to exclude IDH mutation versus when sequencing is also required to classify atumor as IDH wild type.

9/9/2019 10:08 AM

11 Only necessary on first-time diagnoses. 9/9/2019 9:50 AM

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15.63% 5

9.38% 3

Q4 Draft Recommendation Statement 2ATRX status should be assessedin all IDH-mutant DGs unless they show 1p/19q codeletion. (Quality of

Evidence: Moderate; Strength of Recommendation: Strong)Answered: 32 Skipped: 20

TOTAL 32

# COMMENTS DATE

1 "status" is not specific enough IMO. 9/12/2019 5:19 AM

2 I would suggest testing for all DGs in the appropriate clinical and pathologic setting with theexception of 1p/19q codeletion and/or TERT mutation. This may suggest testing for the H3mutations.

9/11/2019 10:10 AM

3 It’s unclear from the recommendations whether the authors wish to promote ATRX testing first, or1p/19q deletion testing first. I have no problem with this recommendation, but it might be helpful toeither recommend which type of testing should come first or state somewhere that the guideline issilent on this matter (which is also fine).

9/11/2019 8:06 AM

4 unneeded 9/10/2019 11:58 AM


6 If one has an IDHmt and no 1p/19q codel what is the added value of atrx? This is probably aboutthe order of assessment, ATRX first or 1p/19q first

9/9/2019 9:27 PM


8 Strength of recommendation: Conditional. Switch this with p53 (see below). The IHC for ATRX isnot as reliable as the one for p53. p53 positivity is better than ATRX negativity. p53 mutation ratein IDH mut diffuse astrocytomas (WHO II-III) is high while ATRX is only in 2/3.

9/9/2019 11:09 AM

9 Agree but would be helpful to state explicitly whether or not IHC is adequate for this. 9/9/2019 10:08 AM

Agree aswritten



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53.57% 15

17.86% 5

25.00% 7

Q5 Draft Recommendation Statement 3TP53 mutation should beassessed in all IDH-mutant DG unless they show 1p/19q codeletion.

(Quality of Evidence: Low; Strength of Recommendation: Conditional)Answered: 28 Skipped: 24

TOTAL 28

# COMMENTS DATE

1 p53 immunostaining is probably useful in IDH-mutant DG, but from my point of view there is nosufficient reason to requestion mutation analysis as a standard (especially, if there is loss of ATRXby immunostaining)

9/11/2019 10:27 PM

2 Recommend in IDH wildtype tumors with Giant Cell Morphology? 9/11/2019 10:10 AM

3 See comments related to Statement 2 9/11/2019 8:06 AM

4 Ability to test TP53 mutation is still in question 9/11/2019 5:29 AM

5 Recommend IHC as accepted method to assess TP53 mutations 9/10/2019 1:33 PM

6 Although it can be moderately helpful and are on most NGS panels, TP53 mutations do not reallyenhance diagnostic classification beyond what IDH and 1p/19q testing can do. Thus, perhaps itshould be "TP53 mutation may be assessed..."

9/10/2019 8:56 AM

7 TP53 needs to be assessed in all cases, otherwise, there is a contradiction with the nextrecommendation!

9/10/2019 5:07 AM


9 Clinical use? 9/9/2019 10:22 PM


11 IHC for all diffuse gliomas. Recommendation: Strong. Take also in consideration this is CAP forthe whole country and not for few academic centers. p53 IHC is available everywhere and is agood stain, easy to read. Make it mandatory.

9/9/2019 11:09 AM

Agree aswritten



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12 Also, agree but would be helpful to state explicitly whether or not IHC is adequate for this andsome basic guidance about what patterns (% expression etc. are appropriate for calling abnormalexpression)

9/9/2019 10:08 AM

13 p53 mutation testing is largely replaced now by ATRX and 1p/19q. It may be of help when ATRX isequivocal and 1p/19q codeletion status is not yet known, but is not necessary for diagnosis.

9/9/2019 9:50 AM

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80.65% 25

9.68% 3

6.45% 2

Q6 Draft Recommendation Statement 41p/19q codeletion status must beassessed in IDH-mutant DGs unless they show ATRX loss or TP53

mutations. (Quality of Evidence: Moderate; Strength of Recommendation:Strong)


TOTAL 31

# COMMENTS DATE

1 still don't like "status". 9/12/2019 5:19 AM

2 See comments related to Statement 1. I believe “should” is the appropriate word, rather than“must.”

9/11/2019 8:06 AM

3 do 1p 19 q first, not last, more diagnostic than the others, who thought this up? 9/10/2019 11:58 AM

4 Perhaps recommendations on the assay would also be helpful. FISH has too many false-positiveresults.

9/10/2019 8:56 AM

5 again, this is about the order of assessment 9/9/2019 9:27 PM

6 This is in conflict with statement 2 & 3. The two statements imply that 1p19q testing should bedone first, which is contarary to CIMPACT-NOW UPDATE 2

9/9/2019 8:55 PM

7 not sure this is relevant for pediatric population 9/9/2019 5:04 PM


9 Agree, as it's obvious this must be done by formal molecular testing. Would clarify again thatATRX loss (or P53 abnormal expression) may be demonstrated by IHC and either of these resultswould enable one not to have to test for 1p19q codeletion.

9/9/2019 10:08 AM

Agree aswritten



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17.86% 5

7.14% 2

Q7 Draft Recommendation Statement 5CDKN2A homozygous deletiontesting may be performed on IDH-mutant diffuse astrocytic gliomas.

(Quality of Evidence: Low; Strength of Recommendation: Conditional)Answered: 28 Skipped: 24

TOTAL 28

# COMMENTS DATE

1 should be performe don IDH mutant diffuse astrocytic gliomas Grade III (mitoses or markedcytological atypia).

9/11/2019 9:39 AM

2 and if found, then what? what impact on grading? 9/10/2019 4:02 AM

3 should be performed?? given the emerging data? 9/9/2019 9:27 PM


5 The quality of evidence for bad prognosis with CDKN2A loss is strong, not low. 9/9/2019 11:09 AM

Agree aswritten



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DisclaimerThe information, data, and draft recommendations provided by the College of American Pathologists are presented for informational and public feedback purposes only.The draft recommendations and supporting documents will be removed on October 7, 2019.The draft recommendations along with the public comments received and completed evidence review will be reassessed by the expert panel in order to formulate the final recommendations. These draft materials should not be stored, adapted, or redistributed in any manner.Not

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12.50% 4

9.38% 3

Q8 Draft Recommendation Statement 6MGMT promoter methylationtesting should be performed on all glioblastomas. (Quality of Evidence:

Moderate; Strength of Recommendation: Strong)Answered: 32 Skipped: 20

TOTAL 32

# COMMENTS DATE

1 I am no authority in this area, and the authors should feel free to disregard this suggestion if I amwrong. Nevertheless, my understanding is that while methylation testing has prognosticsignificance as a standalone test, it is not clear whether it has independent prognostic significancewhen taken in conjunction with IDH testing for the glioblastoma phenotype MGMT testing adds tothe cost of care, and without clear evidence that it provides independent prognostic information Iam wondering whether this should be a conditional recommendation with a “may be performed”instead of a “should be performed.”

9/11/2019 8:06 AM

2 Does this really add necessary information for clinicL management? 9/10/2019 1:33 PM

3 If testing structure easily and cheaply available 9/10/2019 12:14 PM

4 some patients will be palliative 9/10/2019 4:02 AM

5 Is the evidence as compelling for pediatric glioblastomas? 9/9/2019 9:09 PM


7 Neuro-oncologists like this. 9/9/2019 11:09 AM

8 This is very clear and beautifully illustrated on the algorithm. 9/9/2019 10:08 AM

9 Our oncologists also like MGMT to be done on anaplastic astrocytomas as they will have the resultwhen the tumor progresses to GBM without having to wait for a new resection.

9/9/2019 9:50 AM

Agree aswritten



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Q9 Draft Recommendation Statement 7For IDH-mutant DGs of histologicgrade II or III, MGMT promoter methylation testing may not be necessary.

(Quality of Evidence: Low; Strength of Recommendation: Conditional)Recommendation


TOTAL 30

# COMMENTS DATE

1 Many oncologists may not agree with this recommendation as this information is often viewed asimportant for chemotherapy decisions.

9/12/2019 1:11 AM

2 See above 9/10/2019 1:33 PM

3 MGMT is related to treatment success 9/10/2019 11:58 AM

4 It is useful to know if patient's will ultimately respond to chemo 9/9/2019 12:21 PM

Agree aswritten



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83.33% 25

6.67% 2

6.67% 2

Q10 Draft Recommendation Statement 8TERT promoter mutation maybe used to provide further support for the diagnosis of

oligodendrogliomas and IDH-WT glioblastomas. (Quality of Evidence:Low; Strength of Recommendation: Conditional)


TOTAL 30

# COMMENTS DATE

1 and to identify molecular glioblastomas that are histologically Grade III. 9/11/2019 9:39 AM

2 Clarify whether this is necessary rather than “may” be used. 9/10/2019 1:33 PM

3 seldom needed further evidenc 9/10/2019 11:58 AM


5 It means that they will behave more aggressively. It's not necessarily used to support a diagnosis. 9/9/2019 12:21 PM

Agree aswritten



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Agree as written



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80.00% 24

10.00% 3

10.00% 3

Q11 Draft Recommendation Statement 9For histologic grade II-III DGsthat are IDH-WT and H3-WT, whole chromosome 7 gain/whole

chromosome 10 loss or EGFR amplification or TERT promoter testingshould be performed for the molecular diagnosis of a grade IV astrocyticglioma (molecular signature of GBM). (Quality of Evidence: Moderate;

Strength of Recommendation: Strong)Answered: 30 Skipped: 22

TOTAL 30

# COMMENTS DATE

1 However please provide a written clarification as to what is acceptable or ideal to determine wholechromosome 7 gain or whole chromosome 10 loss by FISH the most common way to test for thisand perhaps for other modalities. Similarly for EGFR amplification a clear definition is required todistinguish from polysomy 7. What if there is 5 copies of 7 is that amplification or are you referringto extrachromosmal double minutes or both above a certain copy number?

9/11/2019 6:23 AM

2 Is the really necessary for patient management? 9/10/2019 1:33 PM

3 extraneous, histologic diagnosis, proliferation index related better 9/10/2019 11:58 AM

4 It's fine as is, but perhaps including screening for amplification of other RTKs and MDM2 would behelpful, as well as PTEN mutations rather than just chr10 loss?

9/10/2019 8:56 AM

5 molecular advances are beginning to overtake routinely/widely available testing in clinical labs.Assumes NGS is available in all neuropath centers

9/10/2019 4:02 AM


7 grade IV astrocytic glioma is not a diagnosis within the WHO and this should be mentioned 9/9/2019 9:50 AM

Agree aswritten



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Agree as written



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Q12 Draft Recommendation Statement 10H3 K27M testing must beperformed in diffuse gliomas that involve the mid-line in the appropriateclinical and pathologic setting. (Quality of Evidence: Moderate; Strength

of Recommendation: Strong)Answered: 30 Skipped: 22

TOTAL 30

# COMMENTS DATE

1 "H3 K27M testing" is overly specific jargon. Prefer "Histone H3 mutation testing" 9/12/2019 5:19 AM

2 Specify sequencing vs. IHC techniques. Although some studies suggest high concordancebetween techniques, many molecular neuropathologists don't fully trust IHC for H3 K27M.

9/12/2019 1:11 AM

3 Recommend use of the word “should” rather than “must.” See previous comments. 9/11/2019 8:06 AM

4 But please define midline in your discussion. 9/11/2019 6:23 AM

5 Again, is this really necessary? 9/10/2019 1:33 PM



8 Regardless of patient age 9/9/2019 9:50 AM

Agree aswritten



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10.00% 3

3.33% 1

Q13 Draft Recommendation Statement 11H3 G34 testing may beperformed in children and young adults with IDH-WT DGs. (Quality of

Evidence: Low; Strength of Recommendation: Conditional)Answered: 30 Skipped: 22

TOTAL 30

# COMMENTS DATE

1 "H3 G34 testing" is overly specific jargon. Prefer "Histone H3 mutation testing" 9/12/2019 5:19 AM

2 IDH-WT and ATRX mutant. 9/11/2019 10:10 AM

3 only high grade gliomas 9/10/2019 4:02 AM


Agree aswritten



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Q14 Draft Recommendation Statement 12BRAF mutation testing (V600)should be performed in epithelioid GBMs and DGs of histologic grade II-III that are IDHWT and H3-WT. (Quality of Evidence: Low; Strength of

Recommendation: Strong)Answered: 31 Skipped: 21

TOTAL 31

# COMMENTS DATE

1 Anecdotal data to suggest IHC may not work well in diffuse gliomas. If accurate, a comment in thediscussion might recommend PCR or NGS?

9/11/2019 6:23 AM

2 See above 9/10/2019 1:33 PM

3 the sequence is backward as the idh not needed and the h3wt can be assumed 9/10/2019 11:58 AM

4 specify IHC vs sequencing 9/10/2019 4:02 AM


6 This recommendation is extremely confusing. Specify that this is mainly to differentiate fromganglioglioma, astroblastoma, etc that have BRAF V600 mutation. BRAF V600 mutation isexceeding rare in diffuse glioma, probably only in epithelioid glioblastoma. Unless you want tomake the astroblastoma with BRAF V600E mutation as diffuse astrocytoma. Rather, have NGSperformed on these cases. This will cover all BRAF/RAF1 (not only V600) and also TERT, PTENand EGFR. amplification. My recommendation is to have all H3-wt GBMs and diffuse astrocytomasin adults and kids subjected to NGS. This will cover pretty much everything. Remember that theGBM patients live at best 1 year after the diagnosis. Better make a routine of subjecting GBMcases to NGS with a comprehensive panel. That will keep the confusion down.

9/9/2019 11:09 AM

Agree aswritten



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Q15 Draft Recommendation Statement 13MYB/MYBL1 and FGFR1testing should be performed in children and young adults with DG that

are histologic grade II-III and are IDH-WT and H3-WT. (Quality ofEvidence: Low; Strength of Recommendation: Conditional)


TOTAL 29

# COMMENTS DATE

1 Specify what testing-- mutation testing? 9/12/2019 5:19 AM

2 I believe the word “may” is more appropriate than “should” for conditional recommendations. Agreewith the evaluation about evidence quality and strength of recommendation.

9/11/2019 8:06 AM

3 Not widely available yet. Problematic for general pathologists to execute. some discussion on howthis might be accomplished needed.

9/11/2019 6:23 AM

4 just go straight to the testing without the wild type indication needed 9/10/2019 11:58 AM

5 molecular advances are beginning to overtake routinely/widely available testing in clinical labs.Assumes NGS is available in all neuropath centers

9/10/2019 4:02 AM


7 There are other driver mutations. Perhaps there should be a panel for these cases. 9/9/2019 12:21 PM

Agree aswritten



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Q16 Is this draft guideline recommendation aid helpful?Answered: 31 Skipped: 21

TOTAL 31

# COMMENTS DATE

1 -algorithm is adult centric; ignores histologic grade in guiding molecular testing; confusing visually 9/10/2019 4:07 AM


3 Too complicated for the field pathologist. 9/9/2019 11:15 AM

4 I think this is an incredibly helpful companion to the text of the guidelines. 9/9/2019 10:10 AM

5 The aid has a typo. Under oligos, it should say 6/10 high power fields. This kind of algortihm givesthe impression that the testing is to be done sequentially which would result in a serious delay ofpatient care. Much of these tests can be done at the same time with the aid used upon completionof testing for the integrated diagnosis.

9/9/2019 9:55 AM

Yes

No (pleaseexplain)

Uncertain

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Yes

No (please explain)

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Q17 Do you have any additional comments or suggested modifications forthe draft recommendation aid?


# RESPONSES DATE

1 These recommendations may increase molecular testing, particularly # 5,8,9,11,12,13. We arealso seeing trends toward broad sequencing studies for these tumors.

9/12/2019 1:12 AM

2 1. A general statement would be helpful, if a clear methylome profile may be considered equivalentto direct demonstration of defining molecular alterations. E.g., is the RELA-fusion ependymomaclassification by methylome analysis sufficient or should the RELA fusion be demonstrateddirectly? 2. For histologically grade II/III astrocytomas with EGFR Amplification, TERTp mutation,or +7/-10 copy number alteration, I would prefer the cIMPACT-NOW terminology "diffuseastrocytic glioma, IDH-wildtype, with molecular features...". A staightforward diagnosis ofglioblastoma should be reserved to cases with glioblastoma histology, from my point of view.

9/11/2019 10:34 PM

3 Recommended citation: Schreck KC, Ranjan S, Skorupan N, Bettegowda C, Eberhart CG, AmesHM, Holdhoff M. Incidence and clinicopathologic features of H3 K27M mutations in adults withradiographically-determined midline gliomas. J Neurooncol. 2019 May;143(1):87-93. doi:10.1007/s11060-019-03134-x. Epub 2019 Mar 12. PubMed PMID: 30864101; PubMed CentralPMCID: PMC6482123.

9/11/2019 10:13 AM

4 The NOS and NES entities are not included in the flow chart. some cases that are IDH WT may beglioneuronal - should stain for synaptophysin.

9/11/2019 9:40 AM

5 From Low evidence to strong recommendation in some cases is a bit confusing. 9/11/2019 6:24 AM

6 I think there is a mistake in the section describing the features to be examined in order to upgradethe neoplasm oligodendroglioma WHO grade III. The correct mitotic threshold should be>=6MF/10HPF and not >=6MF/HPF as written.

9/10/2019 10:58 PM

7 There should be some suggestion regarding sequence of molecular testing as the sequentialapproach could take a very long time. The complexity of the algorithm makes it essentiallyimpossible to sign out gliomas outside of tertiary centers. I think it should be greatly simplified toONLY include additional testing that is necessary for patient management and there should be astandard panel of tests that can be ordered initially so that all the results can be made available ina timely manner for a final diagnosis.

9/10/2019 1:38 PM

8 no 9/10/2019 12:14 PM

9 Rethink the significance of the IDH and other ancillary testing as delay and expense are notneeded.

9/10/2019 12:00 PM

10 -algorithm is adult centric; in pediatric tumours you would not start with IDH -need to take gradeinto account in algorithm (high grade more likely H3) -visually confusing: simply into 3 categories:H3, MYB/BRAF/MAPK, molecular GBM

9/10/2019 4:07 AM

11 In the draft the jump is made to include CDKN2A HD as a criterion for astrocytoma WHO grade IV.that could be appropriate but it is not yet official

9/9/2019 9:31 PM

12 a final draft recommendation should include references/resources to explain significance ofdifferent findings

9/9/2019 5:08 PM

13 Tumoral heterogeneity is a huge issue and I think these recommendations need to address themolecular complexities of these tumors. In other words, most of these recommendations do notcapture some of the rare additional driver mutations that these tumor accumulation on account ofreplicative stress. For example, I just recently had a case of a young patient who initially had anIDH-1 mutant (not wildtype) anaplastic astrocytoma and ended up have a MYCN mutation (notamplification) discovered via the FoundationOne panel. He ended up subsequently developing aGBM with a primitive neuronal component. MYCN mutation is seen in less than 0.5% of gliomas,but we would have never have known about this mutation if it were not for the FoundationOnepanel. Perhaps there needs to be a recommendation regarding the utility of such general drivergene panels.

9/9/2019 12:36 PM

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14 I would rather make recommendations what to do with a GBM, a diffuse astro and an oligo, ratherthan put all these markers separately. Basic IHCs (GFAP, IDH, P53 and H3K27M if midline) for all,1p/19q for an oligo-like case, and NGS for all GBMs and diffuse astros. If you want to see CIC andFUBP1 mutations, NGS for all. MGMT for GBM. Done.

9/9/2019 11:15 AM

15 Specific guidance as to when IHC can be used to assess for molecular alterations such as ATRX,IDH would be extremely helpful (either on the visual aid or in the guideline statements).

9/9/2019 10:10 AM

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Q18 How feasible is it to implement this guideline?Answered: 30 Skipped: 22

TOTAL 30

# COMMENTS ABOUT THE FEASIBILITY OF IMPLEMENTING THE GUIDELINE: DATE

1 Other than widespread use of TP53 mutation analysis, the recommendations should be feasible ina setting where glioma patients are treated. The more specialized tests are necessary only in asmall subset of cases so that it should be feasible to outsource them if they are not available in thelocal laboratory.

9/11/2019 10:44 PM

2 Depends on the center and its resources 9/11/2019 10:10 AM

3 I believe these guidelines will challenge the capabilities of some laboratories. However, that shouldnot be a reason to shy away from the recommendations. Diffuse gloom as are not that common,most are seen in well-provisioned facilities, and those that aren’t probably require referral ofhistological material to better provisioned laboratories.

9/11/2019 8:09 AM

4 Needs clarifications/recommendations on appropriate modalities for testing or on those modalitiesthat have limitations.

9/11/2019 6:34 AM

5 many of the mutations are difficult to obtain unless doing next generation sequencing 9/11/2019 5:30 AM

6 Not at all feasible 9/10/2019 1:40 PM

7 1. We currently offer all the tests that are done by Immunohistochemistry in-house. 2. We recentlydiscussed ordering MGMT on all GBMs (recommendation #6). With this recommendation fromCAP, we (pathologists) should be able to automatic order MGMT promoter testing in all GBMs. Wewill incorporate that into our practice. We are also in the process of developing this test in-house.3. Recommendations #5, #8, #9, #11 and #13 require sequencing or DNA-based assays that wewill start developing soon in the new molecular laboratory.

9/10/2019 6:03 AM

8 -assumes NGS will be available -assumes NGS send-out is affordable 9/10/2019 4:09 AM

9 not all molecular tests are available in every lab 9/9/2019 10:24 PM

10 although it supports the use of an efficient single NGS platform to do it all 9/9/2019 9:32 PM

All of it isfeasible to...

Parts of itare feasible...

None of it isfeasible to...

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


All of it is feasible to implement.

Parts of it are feasible to implement.

None of it is feasible to implement.

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11 See my previous comments. 9/9/2019 11:20 AM

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20.83% 5

4.17% 1

25.00% 6

37.50% 9

29.17% 7

12.50% 3

75.00% 18

4.17% 1

20.83% 5

Q19 What barriers might impede adoption of the final guideline? (Chooseall that apply.)Answered: 24 Skipped: 28



Disagreementwith the dra...

Disagreementwith how the...

Too burdensome

Lack ofsupport from...



Lack ofresources...

Do not wish togive up...


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


Disagreement with the draft recommendations

Disagreement with how the guideline was developed

Too burdensome

Lack of support from administration

Lack of support from other members of the medical team

Lack of support from the community (others outside your institution e.g., patients, industry)

Lack of resources (funding)

Do not wish to give up personal autonomy to follow the guideline


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1 Minor discrepancies with WHO/cIMPACT-NOW: - H3 G34 mutation as sufficient for grade IVirrespective of histology - Classification of IDH-wildtye grade II/III astrocytomas should follow eitherWHO or cIMPACT-NOW update 3

9/11/2019 10:44 PM

2 learning new things - old habits die hard; dissemination of information to non academic centers 9/11/2019 10:10 AM

3 Patients may not be able to pay for some of the testing. Genomic profiling may be needed to coversome of the markers like FGFR, MYB.

9/11/2019 6:34 AM

4 Lack of time. 9/9/2019 11:20 AM

5 Test availability 9/9/2019 10:03 AM

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52.00% 13

52.00% 13

40.00% 10

48.00% 12

40.00% 10

20.00% 5

8.00% 2

Q20 What facilitators might assist in your adoption of the final guideline?(Please select your top 3 facilitators.)




1 In smaller populations we need to work collaboratively statewide and set up theseinterconnections to help develop the new testing structures and source funding for items that arenot currently supported by government subsidy

9/10/2019 12:17 PM

2 if guidelines lead to funding 9/10/2019 4:09 AM

If leaders ofthe medical...

If there weretools to hel...

If we areforced to...

If we findthat peer...

If othertrusted...

If we know andtrust the...


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


If leaders of the medical staff discussed adoption/adaption of the guideline for our practice setting

If there were tools to help implement the guideline

If we are forced to comply with the guideline by administration or an accreditation body

If we find that peer institutions/practices adopt the guideline

If other trusted organizations endorse the guideline

If we know and trust the members of the panel members and/or organizations who developed the guideline


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Q21 Please provide any general comments or concerns in the spacebelow:


# RESPONSES DATE

1 In my institution/country it is all a question of funding sources for molecular testing. 9/10/2019 11:03 PM

2 Too complex and to difficult to implement for virtually all pathologists outside of tertiary academiccenters.

9/10/2019 1:40 PM

3 Please see the previous section with my suggestions for a simplified protocol. 9/9/2019 11:20 AM

4 This guideline seems aimed at surgical pathologists who practice occasional neuropathology.Much of this is already being done by neuropathologists. The WHO recognizes oligoastrocytomasof all grades as "exceptional" cases. The first page of this survey listed OA and AOA as diagnoseswith which these recommendations would help (though I didn't see it listed on the aid???). Someclarification, as in the WHO, is in order explaining why these entities are no longer appropriate. Inaddition, I didn't find any place on the algorithm that accounts for what to do with insufficient tissuefor testing or equivocal results. Individuals who would use this guideline will likely do so to theexclusion of other resources as it is meant to be complete in it's recommendation on the work upof DGs. Failure to mention what to do in these circumstances would be a major limitation in thosecases.

9/9/2019 10:03 AM

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40.74% 11

Q22 Do you assess IDHG1/2 in diffuse gliomas?Answered: 27 Skipped: 25

TOTAL 27

# YES - WITH OTHER (SPECIFY) DATE

1 IHC and/or Sanger/next-gen sequencing (as appropriate) 9/11/2019 10:49 PM

2 IHC and then by sequencing if negative on IHC but has both ATRX loss and p53 mutation on IHCor 1p19q co-deletion.

9/11/2019 10:19 AM

3 with IHC if over 60; with sequencing under 60 9/11/2019 10:13 AM

4 IHC first, PCR or NGS as needed 9/11/2019 6:37 AM

5 Both 9/10/2019 5:59 AM

6 if IHC is negative, sequencing 9/9/2019 10:25 PM

7 OncoScan 9/9/2019 12:45 PM

8 both IHC and NGS 9/9/2019 11:24 AM

9 IHC and RT-PCR 9/9/2019 10:55 AM

10 IHC or sequencing if needed 9/9/2019 10:11 AM

11 with either IHC or sequencing depending on the case 9/9/2019 10:05 AM

No

Yes - with IHC

Yes - withSequencing

Yes - withother (specify)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with IHC

Yes - with Sequencing

Yes - with other (specify)

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66.67% 18

11.11% 3

14.81% 4

Q23 Do you test for ATRX on diffuse gliomas?Answered: 27 Skipped: 25

TOTAL 27


1 IHC (+/- next-gen sequencing) 9/11/2019 10:49 PM

2 rare 9/10/2019 12:02 PM

3 both 9/10/2019 5:59 AM


No

Yes - with IHC



0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with IHC



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19

14.81% 4

48.15% 13

14.81% 4

22.22% 6

Q24 Do you assess TP53 status?Answered: 27 Skipped: 25

TOTAL 27


1 IHC (+/- next-gen sequencing) 9/11/2019 10:49 PM

2 IHC primarily, secondarily incidentally with NGS panel sometimes 9/11/2019 6:37 AM

3 both 9/10/2019 5:59 AM

4 OncoScan 9/9/2019 12:45 PM

5 both IHC and NGS 9/9/2019 11:24 AM


No

Yes - with IHC



0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with IHC



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19

3.70% 1

70.37% 19

7.41% 2

3.70% 1

3.70% 1

11.11% 3

Q25 Do you perform 1p/19q testing?Answered: 27 Skipped: 25

TOTAL 27


1 PCR or within methylome analysis 9/11/2019 10:49 PM

2 PCR and NGS 9/10/2019 5:59 AM

3 both FISH and NGS 9/9/2019 11:24 AM

No

Yes - with FISH

Yes - with PCR

Yes - with NGS

Yes - withCytogenomic...


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with FISH

Yes - with PCR

Yes - with NGS

Yes - with Cytogenomic Array


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22.22% 6

40.74% 11

0.00% 0

3.70% 1

25.93% 7

Q26 Do you perform BRAF testing on diffuse gliomas?Answered: 27 Skipped: 25

TOTAL 27


1 IHC and/or Sanger/next-gen sequencing (as appropriate) 9/11/2019 10:49 PM

2 Occasionally by send out in younger, IDHwt patients. 9/11/2019 10:19 AM

3 IHC for V600E and FISH for BRAF duplication; also by NGS secondarily 9/11/2019 6:37 AM

4 sometimes 9/10/2019 12:02 PM

5 IHC AND sequencing 9/10/2019 5:59 AM

6 Both IHC and sequencing 9/9/2019 8:57 PM

7 RT-PCR 9/9/2019 10:55 AM

No

Yes - with IHC


Yes - with FISH

Yes - withCytogenomic...


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with IHC


Yes - with FISH

Yes - with Cytogenomic Array


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3.70% 1

18.52% 5

59.26% 16

3.70% 1

Q27 Do you assess MGMT on glioblastomas?Answered: 27 Skipped: 25

TOTAL 27


1 Send out molecular test 9/10/2019 6:04 AM

No

Yes - with IHC

Yes - withPyrosequencing

Yes - withMethylation...


0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


No

Yes - with IHC

Yes - with Pyrosequencing

Yes - with Methylation specific PCR


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51.85% 14

44.44% 12

3.70% 1

Q28 Do you use multigene panel to assess mutations in diffuse gliomas?Answered: 27 Skipped: 25

TOTAL 27

Yes

No

Uncertain

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


Yes

No

Uncertain

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85.19% 23

0.00% 0

Q29 Do you use Cytogenomic Arrays to assess whole are copy numberin diffuse gliomas?


TOTAL 27

Yes

No

Uncertain

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%


Yes

No

Uncertain

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Q30 What other tests do you routinely perform on diffuse gliomas?(specify)


# RESPONSES DATE

1 Ki-67, GFAP, CD34 9/11/2019 10:49 PM

2 GFAP and OLIG2 expression by IHC. 9/11/2019 10:19 AM

3 Ki67, H3K27M 9/11/2019 10:13 AM

4 GFAP, Ki67, NF, Synaptophysin 9/11/2019 6:37 AM

5 Sometimes us MALDI-TOF Massarray and otherwise refer away 9/10/2019 12:19 PM

6 IHC for IDH in older patients, to avoid the use of expensive NGS 9/9/2019 9:33 PM

7 GFAP, Ki-67! 9/9/2019 11:24 AM

8 Ki-67 9/9/2019 10:05 AM

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September After Valid...1.92% 1 0.00% 0 1.92% 1 1.92% 1 0.00% 0 TOTAL 52 # OTHER (PLEASE SPECIFY)...

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Transcript of September After Valid...1.92% 1 0.00% 0 1.92% 1 1.92% 1 0.00% 0 TOTAL 52 # OTHER (PLEASE SPECIFY)...