Here is the detailed timeline of my husband's diagnosis with GBM. I need help!
My husband is a 47-year old International Airline pilot who was in perfect health prior to his diagnosis in April. After two surgical resections and 6 weeks of RT/TMZ, he is now taking daily TMZ on a metronomic schedule.
| 3/31/18 | Presented with acute aphasia and vision loss, medevacked to Palmetto Richland hospital (Columbia, SC) tumor was discovered in left temporal lobe |
| MRI (missing report details) |
| 4/2/2018 | TRANSPORTED TO MUSC, CHARLESTON, SC |
| 4/4/2018 | SUBTOTAL RESECTION OF LEFT TEMPORAL MASS performed at MUSC, Charleston, SC |
| 4/5/2018 | MRI BRAIN W/WO CONTRAST |
|
Status post subtotal resection of left temporal mass with residual enhancing
tumor along the medial margins of the resection cavity measuring approximately
2.4 x 3.3 cm. Additional enhancing satellite nodule along the posterior
inferior aspect of the resection cavity compatible with residual tumor.
Similar mass effect and partial effacement of the left lateral ventricle with 5
mm rightward midline shift. |
| 4/6/2018 | NEUROPATHOLOGY REPORT - DIAGNOSIS: GLIOBLASTOMA MULTIFORME WHO GRADE IV |
|
(PARTIAL COMMENTS FROM REPORT DATED 4/6/2018)
Date Collected: 4/4/2018 15:05
Diagnosis
A. BRAIN, LABELED AS "TUMOR", RESECTION:
· GLIOBLASTOMA MULTIFORME, WHO GRADE IV
· IMMUNOHISTOCHEMICAL STAINS:
o IDH-1: NEGATIVE
o GFAP: POSITIVE
o SYNAPTOPHYSIN: NEGATIVE
o KI-67: PROLIFERATIVE INDEX OF 10 %
B. BRAIN, LABELED AS "TUMOR", RESECTION:
· GLIOBLASTOMA MULTIFORME, WHO GRADE IV |
| 4/19/2018 | MRI FUNCTIONAL BRAIN |
| 4/20/2018 | MRI BRAIN LAB WITH CONTRAST |
| 4/20/2018 | Surgical Resection performed by Dr. Allan Friedman, Duke |
| Loss of right peripheral vision in both eyes post surgery |
| 4/21/2018 | MRI BRAIN W/WO CONTRAST |
| FINDINGS:
Postoperative changes of left temporal craniotomy with subjacent resection cavity within the left temporal lobe demonstrated. Surrounding increased signal on T2 weighted imaging is unchanged. There are blood products along the margins of the resection cavity. There are small areas of superimposed contrast enhancement along the posterior margin (series 12 image 90),medial margin (series 12 image 95), inferior margin (series 12 image 81), and superior margin (series 12 image 101). The areas of residual contrast enhancement are largely improved from intraoperative MRI. Trace extra-axial fluid and dural thickening at the craniotomy site. There are expected postoperative ischemic changes surrounding the margins of the resection cavity.
No hydrocephalus. The basal cisterns are maintained. Intracranial flow-voids appear normal. The orbits, mastoid sinuses, and visualized paranasal sinuses are unremarkable.
IMPRESSION:
Status post left temporal mass resection with foci of contrast enhancing tumor along the margins of the resection cavity. |
| 5/17/2018 | Day 1 of 6 week Radiation/ Temozolomide therapy (MUSC, Charleston, SC) |
| 6/4/2018 | SEIZURE (occured 2 days after gradually stepping down Dexamethasone to 0mg/day) |
| - MRI & CT scan performed |
| “Postsurgical changes of subtotal resection of left temporal mass with increased size of the resection cavity and likely increased local mass effect with entrapment of the temporal horn of the left lateral ventricle and slightly increased medialization of the left uncus. The component along the resection cavity demonstrating elevated CBV has decreased in size from prior studies.
Overall, these findings are suggestive of evolving post-treatment related changes with persistent residual tumor.Stable 5 mm rightward midline shift.” |
| - Increased dose of Keppra to 1g 2x day |
| - Increased Dexamethasone to 6mg 2 x day (to gradually step back down) |
| 6/8/2018 | MGMT GENE METHYLATION ASSAY - “GENE METHYLATION NOT DETECTED” |
| 6/8/2018 | PATHOLOGY - GENERAL/OTHER - “ NEGATIVE FOR IDH1 R132H MUTATION” |
| 6/27/2018 | Completed 6 weeks of Radiation/ Temozolomide treatment |
| 7/11/2018 | SEIZURE (occured 2 days after gradually stepping off dexamethasone) |
| - MRI & CT scan |
| “ADDENDUM: Similar appearance of a linear area of incomplete filling in the posterior superior sagittal sinus. This has been present on multiple prior studies, including the patient's original outpatient imaging and may reflect an underlying dural reflection or potentially chronic sequela of remote partial filling defect. No occlusion of the sinus flow is seen.
IMPRESSION: Posttreatment changes from subtotal resection of left temporal mass with persistent residual tumor and slightly decreased size of the resection cavity.Slightly increased vasogenic edema predominantly along the left insular region. Stable 5 mm rightward midline shift and early left uncal herniation.
No acute infarction.” |
| - Increased Keppra to 1500mg 2 x day |
| - Increased Dexamethasone back to 6mg 2 x day |
| 7/13/2018 | FOOT DROP IN LEFT FOOT (possible stroke during seizure, MRI of spine schedules for end of month) |
| 7/27/2018 | MRI BRAIN W/WO Contrast |
| “Extensive irregular enhancement of the resection cavity extending to the ependymal surface of the left lateral ventricle, appearing slightly increased in size. Significant increase in relative CBV within areas of enhancement and nonenhancing T2 hyperintensity. There has however been interval reduction of overall mass effect and rightward midline shift.” |
| 8/1/2018 | DAY 1 METRONOMIC TEMOZOLOMIDE (100MG/DAY) |
| STARTED DISULFIRAM 250MG/DAY + COPPER 2MG/DAY |
MEDICATIONS & SUPPLEMENTS:
NO Rxs:
- Keppra: 1500mg 2 x day (dose has increased 2 x after seizures)
- Dexamethasone: 6mg / day. (dose has varied due to seizures)
- Temozolomide: 100mg daily (metronomic schedule)
OFF LABEL RXs:
- Minocycline: 100mg 2 x day (May 17 - present)
- Metformin; 500mg 3x day (escalted to current dose starting May 17th)
- Chloroquine: 250 mg (May 17 - present)
- Disulfiram: 250mg / day (August 1 - present)
SUPPLEMENTS:
- Copper: 2mg (taken with Disulfiram)
- Milk thistle: 1000mg 2 x day
- Curcumin (Longvida): 1600mg / day
- Fish Oil: 1000mg / day
- Boswellia: 3g / day
- Turkey Tail (PSK): 3g/day
- Soy Isoflavones (Genistein, Daidzein, Glycitein) ?mg. 3 gelcaps/day
- Melatonin: 20mg at bedtime
- Vitamin D3: 10,000 IU/day
- Selenium: 200mcg / day
- Pterostilbene: 450mg / day
- Green Tea Extract: 750mg 3 x day
- CBD oil (Palmetto Harmony): 1ml 2 x day
QUESTIONS:
1. MEDICATIONS AND SUPPLEMENTS: Are there any others medications or supplements I should add to his cocktail at this point (currently
doing 100mg temozolomide, daily)
- Celebrex? I had this on my list, but I had trouble filling the Rx
- THC ? He is currently taking CBD oil, but wanted to refrain from the THC bc he is still an active Reservist in the US AF.
2. Dexamethasone - We have tried taking him off steroids twice, both times resulting in seizure. I have read that dexamethasone can inhibit the effectiveness of chemotherapy, but he obviously continues to struggle with swelling. Any thoughts?
3. UNDERSTANDING THE PATHOLOGY, BRAIN BIOMARKERS, ETC
- MGMT GENE METHYLATION ASSAY - “Gene Methylation NOT detected” = UNMETHYLATED
- NEUROPATHOLOGY REPORT:
Date Collected: 4/4/2018 15:05
Diagnosis
A. BRAIN, LABELED AS "TUMOR", RESECTION:
· GLIOBLASTOMA MULTIFORME, WHO GRADE IV
· IMMUNOHISTOCHEMICAL STAINS:
o IDH-1: NEGATIVE
o GFAP: POSITIVE
o SYNAPTOPHYSIN: NEGATIVE
o KI-67: PROLIFERATIVE INDEX OF 10 %
MICROARRAY COMMENT:
1p/19q co-deletion - Not detected
+7/-10 - DETECTED
CDKN2A/B homozygous deletion - DETECTED
EGFR amplification - Not detected
- BRAIN BIOMARKERS (IHC, FISH):
- IDH1: NEGATIVE, R132H IDH1 MUTATION WAS NOT DETECTED.
- EGFR does not exhibit amplification.
- EGFR RECEPTOR IHC ANALYSIS:Approximately 50% of the tumor cells exhibit 2+ staining of their cell membrane (score 2+), indicating that they DO express epidermal growth factor receptor.
- EGFR VIII IHC Analysis: none of the tumor cells exhibit staining for EGFR VIII (Score= 0)
- IDH1 IHC Analysis:IDH1 mutations result in a histidine at codon 132. An antibody specific for the IDH1-R132H mutation is NEGATIVE
- Brain IHC Analysis:
D2C7 IMMUNOHISTOCHEMISTRY ANALYSIS:
Approximately 70% of the tumor cells exhibit D2C7 detectable EGFR staining of their cell membrane (score 2+), indicating that they DO express at least some portion of the epidermal growth factor receptor protein.
POLIOVIRUS RECEPTOR (PVR) IMMUNHISTOCHEMTRY:
Approximately 90% of the tumor cells exhibit 2+ staining of their cell membrane (score 2+). The endothelial cells stains positively (3+) and serves as a internal control.
- TERT TARGETED MUTATION ANALYSIS: Positive.
TERT promoter mutation detected (C228T, c.-124C>T).
CAN SOMEONE PLEASE HELP ME UNDERSTAND THESE FINDINGS?
I understand the implications of his tumor being UNMETHYLATED, but I am struggling to understand the rest of it.
Also, I am waiting on the results from Foundation One, and hope those results prove useful.
