tumor board session - cme.cityofhope.org
TRANSCRIPT
TUMOR BOARD SESSION
COMPLEX CASES: OPTIMAL MANAGEMENT
OF BRAIN METASTASES
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Panel & Disclosures
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Arya Amini, MDAssistant Professor
Department of Radiation OncologyChief of Thoracic Radiotherapy
City of Hope
• Grant/Research Support from Genentech.• Consultant for Reflexion.• On the Speakers Bureau for AstraZeneca, and
Takeda Pharmaceuticals.
Mike Chen, MD, PhDAssociate Professor
Department of SurgeryProgram Director
Neurosurgical Oncology Fellowship ProgramCity of Hope
• Nothing to disclose.
N. Simon Tchekmedyian, MD, FACPProfessor
Department of Medical OncologySenior Medical Director, Orange County
City of Hope
• Stock/Shareholder for BioMarin Pharmaceuticals, Infinity Pharmaceuticals, Inc., Mereo BioPharma Group, Mersana Therapeutics, Inc., Myovant Sciences, and Novo Nordisk.
Case #1: Young Woman With Lung Cancer
▪ 43 year old woman, never smoker, presented elsewhere in April 2011 with persistent nausea and incidental finding of right lower lung nodule.
▪ Biopsy revealed adenocarcinoma.
▪ Right lower lobectomy showed pT1a pN2 lesion (3 + nodes, one in level 4 and 2 in level 7) adenocarcinoma, acinar predominant, with clear margins except that parenchymal margin was positive for tumor cells in lymphatic spaces. EGFR negative. ALK alteration not tested.
▪ Received Carboplatin and Pemetrexed for 4 cycles and was then observed.
▪ In November 2013 a right hilar mass showed adenocarcinoma on core biopsy.
▪ She received Carboplatin, Paclitaxel and radiation therapy with partial response on imaging
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Patient Seen For Opinion
▪ Consultation done March 2014. Given the presentation, Alk alteration testing requested and
found to be positive.
▪ Crizotinib was recommended but patient declined in part because a “DetoxiGenomic” test
profile suggested she would not tolerate it.
▪ She returned in April 2016. She had started Crizotinib due to lung progression 18 months
earlier and now had lung progression as well as symptomatic brain metastases: 15 supra and
infratentorial lesions, largest 6.7 cm, and midline shift.
▪ Had neurosurgery with resection of largest left temporal lesion and whole brain RT
▪ Patient changed care to our program and Alectinib was started. Alectinib had been approved by
the FDA in December 2015 for patients who progressed on Crizotinib.
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Subsequent Care and Current Status
▪ On Alectinib for 2 and ½ years, lung progression in November 2018.
▪ Entered on expanded access protocol for Lorlatinib, Cycle 1 Day 1 on 11/15/2018. Had
favorable response. Subsequently went on commercial Lorlatinib and has stayed on it until
present time.
▪ Developed hydrocephalus without tumor recurrence and had VP shunt placed in March 2021.
▪ Remains on Lorlatinib with disease control and preserved cognition.
▪ MRI brain in June 2021 showed improved hydrocephalus and no evidence of brain metastases.
▪ CT chest/abdomen/pelvis in June 2021 showed no evidence of recurrent or metastatic disease.
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From Left: 1) MRI at diagnosis, 2) Immediate post-op, and 3) Over 5 years
later, after RT, targeted oral therapies and recent VP shunt
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7
Month
Treatment carbo/pem
Molecular ALK FISH negative
CGP
ALK intron 19
TP53 G154V and R158C
RB1 loss of exons 3-17
crizotinib ceritinib
CGP
ALK intron 19ALK L1152R
TP53 G154V and R158C
RB1 loss of exons 3-17
NF1 G1852fs*17
WBRT alectinib
ALK D5F3 IHC positive
Response SD PR PD PRPD + newCNS metastases PR
2 4 6 8 10 12 140 16
A B
C D
Figure 1. The top panel displays the chronology of treatment, response and molecular pathology. The bottom-right panel shows serial CT chest/abdomen with intravenous contrast A) pre- alectinib, and B) 6 weeks post-alectinib; and serial CT brain with and without contrast, C) pre-alectinib, and D) 6 weeks post-alectinib. Red arrows point to areas of disease and subsequent response. CT, computed tomography; SD, stable disease; PR, partial response; PD, progressive disease; CNS, central nervous system; ALK, anaplastic lymphoma kinase; FISH, fluorescent in situ hybridization; RB1, retinoblastoma-1; TP-53, tumor protein-53, NF-1, neurofibromin-1; CGP, comprehensive genomic profiling; IHC, immunohistochemistry; WBRT, whole brain radiation therapy; carbo, carboplatin; pem, pemetrexed.
Tchekmedyian JTO 2016
Month
Treatment Poziotinib 16mg PO Daily
Molecular
Pause
Response PR PD-lung only Flare Flare
2 3 4 5 6 70 8
B
C D
Figure 1. Chronology of treatment, response, molecular pathology and imaging. Panel A shows the pre-treatment baseline scan, panel B shows the 4 week post-poziotinib scan, panel C represents the flare 3 weeks after poziotinib discontinuation, panel D shows the treatment response after re-initiation of poziotinib on the EAP, panel E shows the second flare two weeks after discontinuing the poziotinib EAP. cfDNA, cell-free DNA; CT, computed tomography; D/C, discontinued; EAP, expanded access program; MR, magnetic resonance imaging; PR, partial response; PD, progressive disease; CGP, comprehensive genomic profiling.
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Poziotinib 12mg PO Daily
PR
Plasma cfDNA CGP Pre-treatment Month 9
ERBB2 (HER2) A775_G776insYVMA (Exon 20 insertion)
13.5% (variant allele fraction) 35.3%
EGFR Amplification Not Detected 2.5 (plasma copy number)
A) 12/10/18 MR B) 1/9/19 MR C) 6/21/19 MR D) 7/18/19 MR E) 9/28/19 CT
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D/C
Tchekmedyian JTO CRR 2020
Discussion Points on Case 1
▪ Molecular testing in NSCLC
▪ Role of Systemic Therapy and intracranial response
▪ Role of Surgery for brain metastases
▪ Role of Radiation for brain metastases
o SRS vs Whole Brain
▪ Timing of surgery and/or radiation
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Case #2
▪ 78 year old female with newly diagnosed NSCLC
▪ Began having falls and left-sided weakness
▪ CT of the brain showed multiple sizable tumors, one in the right anterior frontal convexity and
the other in the right posterior frontal/anterior
▪ CT scan of the chest abdomen and pelvis which showed evidence of a 3.3 cm central left upper
lobe lung mass with a large left pleural effusion and left lung atelectasis.
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Case #2
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Case #2
▪ HopeSeq
▪ Adenocarcinoma
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Case #2
▪ Post-Surgical
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Case #2
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Case #3
▪ 34 yo female with metastatic cutaneous BRAF mutant melanoma initially diagnosed in 7/18/11 with punch biopsy of right lower extremity skin lesion. She completed 6 months of adjuvant interferon alpha on 03/09/12. Remained clinically without evidence of disease until 9/17/18, when PET CT showed a new FDG avid 1.6 cm Left lower lung nodule. This was followed by u/s right groin area due patient palpated enlargement, which was confirmed right inguinal adenopathy.
▪ She underwent thorascopic wedge resection on 10/10/18 demonstrating a 1.8 cm tumor involving the lung parenchyma of left lower lobe, which was positive for metastatic melanoma, (2/2) lymph nodes also positive. She completed 3/4 planned cycles of ipilimumab plus nivolumab on 12/03/18. 4th cycle cancelled due to urosepsis and autoimmune hepatitis. She then developed recurrence in the left posterior chest wall in October 2019, and underwent left chest wall excision on 1/10/20, followed by radiation to the area.
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Case #3
▪ Underwent SRS 2/20 presents to
COH in 5/20 and within a 2-3
weeks was admitted with altered
mental status and seizures. MRI
revealed a hemorrhagic right
temporal lesion, (previously
treated), increasing in size.
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Case #3: Pre and postop MRI from may 2020
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Case #3:
Craniotomy #2: developed multiple brain mets
Despite SRS, lesions progressed by July 2020
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Case #3
▪ With multiple brain lesions and suspected LMC, craniotomy would not be a conventional option.
▪ A shunt and Ommaya reservoir were inserted shortly after the craniotomy.
▪ These were followed by whole brain XRT in 8/2020.
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Case #3
▪ IT nivolumab given at end of 8/2020.
▪ She initiated pembrolizumab, given every 3 weeks, on 10/19/20, and has now received a total
of 5 cycles. She was also taking encorafenib 450 mg daily with binimetinib 45 mg by mouth 2
times a daily, concurrently with pembrolizumab.
▪ SRS to multiple brain lesions (PTVs 6-9) from 6/2/21 - 6/11/21
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Case #3: MRI 8/21
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NERSES SIMON TCHEKMEDYIAN
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ARYA AMINI
MIKE CHEN
Questions