VUmc SABR Symposium 2017 Treatment of Multiple Lung Tumors Indications and Dosimetric Considerations Dr. David Palma, MD, MSc, PhD Radiation Oncologist, London Health Sciences Centre Clinician-Scientist, Ontario Institute for Cancer Research London, Canada
Before We Start Two things are needed to contour: Image dataset Folder with DICOM files Contouring program ITK SNAP
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Triple Trouble 85 year-old man with prior history of a T3N2c squamous cell carcinoma of the supraglottis treated with chemoradiation in 2010. Presented in May 2017 with a cough. CXR showed nodules in right lung and CT scan ordered. goo.gl/ui1v4c
Triple Trouble None were present in 2010. Left-sided lesion arising within a previous cyst. goo.gl/ui1v4c
Triple Trouble Medical History: Type 2 diabetes (not on insulin), GERD, HTN, angina, hypothyroidism, depression, mild cognitive impairment Social History: 80 pack-year history of smoking, quit 30 years ago
Triple Trouble Referred to Thoracic Surgery PFTs: mild airflow obstruction Offered observation or referral to Radiation Oncology
Triple Trouble Repeat CT September 2017 showed increase in size in all 3 lesions RUL 0.8 to 1.3 cm RML 1.2 to 1.7 cm LLL 1.4 to 1.7 cm There are 3 separate lung lesions which have been slowly growing, none of which were present in September, 2010. They all look concerning for synchronous bronchogenic carcinomas.
PET/CT All 3 lesions are hot on PET: SUVmax 5.9-9.4 Underlying primary lung neoplastic process versus metastatic lesions cannot be distinguished
What is going on?? 3 metastases from laryngeal cancer 3 lung primaries 2 lung primaries with 1 metastasis (from lung or larynx) 1 lung primary with 2 metastasis Summary: Oligometastatic disease or 3 primary lung cancers
Martini and Melamed Criteria J Thorac Cardiovasc Surg 1975
Genomic Profiling Genomic profiles analyzed from 15 lung adenocarcinomas in 6 patients All suggested independent primary tumors (not metastases) Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Nature Communications 2016
Genomic Profiling
IASLC It is easier to determine that two tumors are different than that they are the same; finding similarities does not establish that they are the same. Few features are definitive; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification.
IASLC Clinical Criteria
Back to the Case It was decided at our multidisciplinary tumor board that the most likely scenario is that these lesions represent 3 primary lung tumors Herder risk calculator: each nodule >95% doesn t even take into account synchronicity or growth In light of the high PET avidity and Herder score, treatment without biopsy was considered reasonable
Multiple Targets: Dose Constraints? Hanna et al, Clin Oncol 2017
Data: Multiple Lung Targets 101 patients, 39 synchronous, 62 metachronous (>6 months apart). First lesion: 29 SABR, 25 conventional RT, 42 surgery, 5 surgery + PORT Second lesion: 101 SABR Treated with 50 Gy in 4 fractions (or 70 Gy in 10 fractions if dose constraints not met)
Outcomes 4 year in-field local control 95.7%
Outcomes: Toxicity
SABR for Synchronous Lesions 84 patients with 188 lesions treated with multiple isocentres, from 2 institutions Most patients (97%) with 2-3 lesions. Median total PTV size: 52 cc Fractionations: 34/1, 54/3, 55/5, 60/8 Acta Oncologica 2016
SABR for Synchronous Lesions
Dosimetry: EQD2
SABR for Synchronous Lesions Toxicity 20% Grade 2+ RP (11%), chest wall (6%) 2% Grade 3 1 patient with possible Grade 5: bilateral pneumonia
Prediction of Toxicity EQD 2 35 Gy = BED 3 58.5 Gy 3 fractions: V19 < 6.5% 5 fractions: V23 < 6.5% 8 fractions: V27 < 6.5%
Critical Volume Concept Rough rule of thumb: For a parallel organ, keep a certain amount of the organ (approximately 1/3) preserved NRG protocols, and others, define threshold doses for 1500 cc and 1000 cc of lung
Critical Volume Concept
Critical Volume Concept CV12.5 = volume receiving 12.5 Gy or less 5 fractions: 1.5 L receiving <12.5 Gy
Our Case: PTVs in Red
Our Case: Dose
Our Plan Goal: 1500 cc with a critical volume threshold of 14.3 Gy (8 fractions) Each PTV optimized separately. There was some contribution across plans, so each PTV was optimized to be under-covered; good coverage on composite plan
Multiple Lung Targets: A Hot Topic
Expert Opinions Bilateral VATS vs. sternotomy is the surgical dilemma. This case is not in the gray zone. The patient has incurable metastatic disease and should not have further meddlesome local therapy, unless symptomatic.
Expert Opinions Our preference would be to recommend initial systemic chemotherapy if SABR is chosen as initial therapy we would recommend 60 Gy in 8 fractions to the left and 54 Gy in 3 fractions to the right
What Really Happened
TROG 13.01
What Really Happened
Take Home Messages When histology is the same, it is difficult to determine if multiple lung lesions are primary tumors or metastases. Early genomic data suggests that multiple primaries are common. SABR of multiple lesions is feasible. Dose constraints not well-determined Early studies suggest toxicity is reasonable
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