Evaluation of Transscleral Versus Transvitreal Biopsy Timothy G. - - PowerPoint PPT Presentation

Uveal Melanoma Fine Needle Aspiration Biopsy (FNAB) for Molecular Genomic Classification: Evaluation of Transscleral Versus Transvitreal Biopsy Timothy G. Murray, MD MBA FACS

Miami Ocular Oncology and Retina (MOOR) Miami, Florida ASRS 2018 Vancouver, British Columbia

Disclosures

• No Relevant Disclosures
• Consultant for Alcon Surgical
• IST Funding Regeneron

Uveal Malignant Melanoma Management

• Globe Conservation – Standard of care utilizing either

radiotherapy for Medium/Large Melanoma or Directed Surgical Ablation for Small Melanoma

• Radiation retinopathy – Virtually 100% of all

macular/juxtapapillary tumors

• Molecular Genomics – Chromosomal analysis, GEP

RNA screening, biopsy sampling, practical implications

DecisionDx-UM

• Castle Biosciences – Validated, CLIA

approved

• RT-PCR 15 Genes (3 control genes)
• CDH1,ECM1,

EIF1B,FXR1,HTR2B,ID2,LMCD1,LTA4H MTUS1,RAB31,ROBO1, and SATB1

• Learning algorithm (SVM)
• Predicted classification AND discriminant value

DecisionDx-UM

• Validation Studies
• Worley et al, Clinical Cancer Research, 13(5): 1466-1471,

2007 Comparison Gene Expression Profiling to Monosomy 3 67 patients Monosomy 3 FISH/aCGH, SNP-LOH ONLY Gene expression profile (P<.0001) and tumor size (P<.02) were independent contributors to prognosis

Molecular Signature Class

Metastasis Free

Class 3 year 5 year Class 1A 98% 98% Class 1B 93% 79% Class 2 50% 28%

Censored data 6/9/2011 514 patients p<.0001

FNAB Molecular Genomics Study Purpose

• To evaluate the impact and outcomes

for two different biopsy approaches for molecular diagnostic testing of uveal melanoma: Trans-scleral versus Trans- vitreal

Study Methods

• Institutional review board approved, single surgeon,

retrospective review of a prospective, consecutive case series of 353 eyes of 353 patients with posterior uveal melanoma.

• All eyes biopsied either at the time of primary

brachytherapy or during primary/secondary MIVS melanoma treatment.

• All FNAB specimens were processed for uveal melanoma

diagnostic testing using a standard processing approach and all testing was completed with a single laboratory (Castle Biosciences, Inc.).

Patient Data

• 353 patients (353 eyes)
• Age (mean):

69 years (17 to 89 years)

• Sex:

187 women/166 men (53% women)

• Mean follow-up:

46 months (20 to 74 months)

Trans- Scleral Biopsy Technique

• 25 gauge needle
• Oblique insertion
• Multiple Pass
• High aspiration
• Inspect biopsy site and immediate brachytherapy application
• Intra-operative echographic evaluation

Trans-Vitreal MIVS Biopsy Technique

• 23/25+ gauge MIVS pars plana vitrectomy
• Remove hyaloid
• Remove vitreo-retinal traction overlying tumor
• Direct endo-laser confluent tumor treatment
• 25 gauge needle
• Multiple needle passes within the tumor
• Inspect for bleeding
• Intravitreal triamcinolone acetonide

Sample Handling

Uveal Melanoma GEP Study Results

• 353 Biopsies/353 Eyes
• Mean follow-up:

46 months (20 to 74 months)

• Biopsy Approach:
• Trans-vitreal:

216 eyes (216/353, 61.2%)

• Trans-scleral:

137 eyes (137/353, 38.8%)

• GEP Analysis:
• Determinant Biopsy

333 eyes (333/353, 94.3%)

• Multiple Gene Failure

20 eyes (20/353, 5.6%)

• GEP Failure Assessment:
• Trans-scleral

2 eye (2/137, 1.7%)

• Trans-vitreal

18 eyes (18/216, 7.3%)

• GEP Failure - Excessive Fluid 10 eyes

(10/20, 50%)

Uveal Melanoma GEP Study Results

Complications

• Vitreous Hemorrhage

8 eyes (8/353, 2.3%)

• Progressive Retinal Detachment

5 eyes (5/353, 1.4%)

• Trans-scleral Biopsy

1 eye (1/137, 0.7%)

• Trans-vitreal Biopsy

4 eyes (4/216, 1.9%)

Potential Issues

• Tumor Recurrence

0 eyes (0/353, 0%)

• Extra-ocular Extension

0 eyes (0/353, 0%)

• Hypotony

0 eyes (0/353, 0%)

• Endophthlamitis

0 eyes (0/353, 0%)

Uveal Melanoma GEP Study Results

GEP Classification Overall

• Class1

251 eyes (251/353, 71.1%)

• Subclass 1a

78 eyes (78/251, 31.1%)

• Subclass 1b

173 eyes (173/251, 68.9%)

• Class 2

82 eyes (82/353, 24.6%)

Conclusions

• Fine needle aspiration biopsy performed via a trans-scleral OR

trans-vitreal multi-pass approach achieves molecular classification in greater than 95% of all patients undergoing treatment for uveal melanoma independent of tumor size

• Complications related to FNAB using these techniques are rare

but may be both anatomically and visually compromising

• Ultimately, genomic profiling is both feasible and informative

allowing tumor risk assessment, targeted patient follow-up and consideration of adjunctive therapy

Potential Limitations

• Single institutional study
• Single surgeon (TGM)
• Sample size (353 patients)
• F0llow-up (46 months)

Thank you!

• Dr. Victor Villegas
• Dr. Aaron Gold
• Azeema Latiff
• Fiona Ehlies
• MIAMI OCULAR ONCOLOGYand RETINA (MOOR)

Genomics Case Series Clinical Pearls

• Utility of genomic profiling in my clinical practice
• Class 2 patients undergo enhanced metastatic screening
• Class 2 patients offered adjunctive systemic therapy
• Valproic Acid (DEPAKENE)
• Ipilimumab (YERVOY)
• Class 1 patients stratified by subclassification
• Class 1b followed with standard of care
• Class 1a offered reduced screening