Can Radiotherapy Cure Stage IV Cancer? The Future of Oligometastatic - PowerPoint PPT Presentation

Can Radiotherapy Cure Stage IV Cancer? The Future of Oligometastatic Cancer Julian Hong, MD MS Felix Feng, MD Department of Radiation Oncology University of California at San Francisco

Disclosures • FF has served on advisory boards for Astellas, Bayer, Blue Earth Diagnostics, Celgene, EMD Serono, Janssen, Myovant, Roivant, and Sanofi. • FF has consulted for Clovis and Genentech. • FF serves on the Scientific Advisory Board of SerImmune. • FF is co-founder of PFS Genomics, a molecular diagnostic company in breast cancer • JH has a pending patent, 62/809,014 “Systems and methods for predicting acute care visits during outpatient cancer therapy”

Roadmap • What is radiotherapy? • What is (oligo)metastatic cancer? • Principles of treatment • Radiation for oligometastasis • Prostate cancer: a case study • Studies on the horizon

Roadmap • What is radiotherapy? • What is (oligo)metastatic cancer? • Principles of treatment • Radiation for oligometastasis • Prostate cancer: a case study • Studies on the horizon

What is radiotherapy? • About half of cancer patients will receive radiotherapy 1 • Part of curative treatment for many cancers • Can be in conjunction with surgery or chemotherapy Image source: NCI 1. Delaney et al. Clin Oncol. 2015.

What is radiotherapy? • About half of cancer patients will receive radiotherapy 1 • Part of curative treatment for many cancers • Can be in conjunction with surgery or chemotherapy Image source: Accuray 1. Delaney et al. Clin Oncol. 2015.

What is radiotherapy? • About half of cancer patients will receive radiotherapy 1 • Part of curative treatment for many cancers • Can be in conjunction with surgery or chemotherapy 1. Delaney et al. Clin Oncol. 2015. Image source: NCI

What is radiotherapy? • About half of cancer patients will receive radiotherapy 1 • Part of curative treatment for many cancers • Can be in conjunction with surgery or chemotherapy 1. Delaney et al. Clin Oncol. 2015.

Roadmap • What is radiotherapy? • What is (oligo)metastatic cancer? • Principles of treatment • Radiation for oligometastasis • Prostate cancer: a case study • Studies on the horizon

Chang and Massague, N Engl J Med. 2008 Dec 25;359(26):2814-23

Widely Metastatic Disease Limited Metastatic Disease

What is oligometastatic cancer? • An intermediate state of Typically defined as 1-5 metastases cancer spread between localized disease and widespread metastases • Proposed as a distinct clinical state by S Hellman and R Weichselbaum Figure courtesy of Phuoc Tran

Hellman and Weichselbaum, J Clin Oncol 1995

Based on Imaging… Widely Metastatic Disease Limited Metastatic Disease • Changing imaging modalities • Breast (PET not routine) • Lack of benchmark gold standard

Imaging and detection are also getting better!

Why the Oligometastatic Space has Increased in Prostate Cancer: The Advent of PET Imaging Increasing Use of PSMA PET: Melbourne 120 Increasing Use of PSMA PET: San Francisco 100 NaF Chol PSMA 80 60 40 20 0 6 6 6 6 6 6 7 7 7 7 1 1 1 1 1 1 1 1 1 1 / / / / / / / / / / 1 1 1 1 1 1 1 1 1 1 / / / / / / / / / / 2 4 6 8 0 2 2 4 6 8 1 1 BCR PreRP Figure courtesy of Michael Hofman, Peter MacCallum Cancer Center, Melbourne Figure courtesy of Thomas Hope, UC San Francisco Axumin (fluciclovine F18) PET: Currently available at hundreds of imaging sites across the US FDA–approved for use in biochemical recurrence, reimbursed by Medicare and some private payers

Using Advanced PET Imaging to Detect Extrapelvic Disease in Patients with PSA Recurrences Fluciclovine F18 PET Gallium 68 PSMA PET PSA levels Bach-Gansmo T, et al. J Urol 2017;197:676-83 Boreta L et al, Urology 2019; 129 (165-171)

PSMA vs Fluciclovine PET Inter ‐ reader variability (k) PSMA Fluciclovine 0.67 0.20 Calais et al, Lancet Oncology 2019

PSMA PET Identifies Oligometastatic Disease at Low PSA Recurrences • UCSF Experience using PSMA PET at time of recurrence 125 men with BCR after • prostatectomy (PSA <2) • 53% had a PSMA ‐ avid lesion • 38% had a lesion outside of the pelvis 30 % had a lesion outside • of a standard RT field Boreta et al, Urology 2019

Are there different types of oligometasis? • Extent • Time • Treatment

Types of oligometastasis Guckenberger et al. Lancet Oncol. 2020.

Types of oligometastasis Hortobagyi et al. J Clin Oncol. 1983.

The Evolution of Metastatic Disease • Both the primary tumor and existing metastases can seed new metastases. • The principal mode of spread is metastases to metastases. • Thus, to cure oligometastatic disease, one may need to ablate both the primary and the metastases. Gundem et al (Bova), Nature 2015

(Some) oligometastatic patients have indolent disease 619 anthracycline treated patients, Minimum f/u 4 years Hortobagyi et al. J Clin Oncol. 1983.

More limited progression • Typically in the same organ • 89% of cumulative new metastases • Milano et al. Am J Clin Oncol . 2010. • Typically few in number • 72% progress in 1-3 new metastases • Salama et al. Cancer . 2012.

Survival Radi Radiati ation (SBR n (SBRT) treat treated d oligome oligometasta astases: ses: Patt tterns of erns of dif differentially e erentially expressed miRs c pressed miRs correlat rrelate with phen with phenotype and sur e and surviv ival al Polymetastatic Oligometastatic cluster cluster (net up-regulation (net down-regulation of miRs) of miRs) Lussier et al. PLOS ONE. 2011.

Roadmap • What is radiotherapy? • What is (oligo)metastatic cancer? • Principles of treatment • Radiation for oligometastasis • Prostate cancer: a case study • Studies on the horizon

How do we treat metastases? • Systemic therapy • Surgery • Radiation • Conventional radiation • Stereotactic radiation (SBRT/SABR) • Ablation

Metastasectomy • Associated with improved outcomes • Series focus on specific sites of metastasis Pastorino et al. J Thorac Cardiovasc Surg. 2011.

Radiofrequency ablation • Colorectal cancer • Liver metastases only • Systemic therapy • With or without ablation Pastorino et al. J Thorac Cardiovasc Surg. 2011.

Roadmap • What is radiotherapy? • What is (oligo)metastatic cancer? • Principles of treatment • Radiation for oligometastasis • Prostate cancer: a case study • Studies on the horizon

Stereotactic body radiation therapy (SBRT) • Used for lung, pancreas cancers • Oligometastases • Precise, image- guided, high dose radiation in few treatments Hong and Salama. Cancer Treatment Reviews. 2017.

Pooling early studies

Pooling early studies 1.00 +++ ++ + + + + + + + + + + + + ++ + ++ + + + + + + + ++ + + + + + + + + + + + + + + ++ + + + ++ + ++ + + + + All patients 0.75 + + + + + + + + + + + + + + + + + +++ + + + + + ++ + + + Overall survival + + + ++ + + + + + + ++ + + + + + + Strata Breast Other primary + + + + + + Class 1 + + + + + + + Kidney + + + + + ++ + + + Class 2 0.50 Prostate + + Class 3 + + + + + + + Class 4 + Time to metastasis Time to metastasis + ++ ++ + + + + Class 5 + +++ + ≥ 75 months < 75 months + + + + 0.25 # metastases ≤ 2 # metastases >2 + + Age ≤ 61 Age > 62 0.00 Class 1 Class 2 Class 3 Class 4 Class 5 n = 92 n = 13 n = 189 n = 37 n = 30 0 12 24 36 48 60 72 Time (months) 3-year OS 75% 3-year OS 85% 3-year OS 55% 3-year OS 38% 3-year OS 13% 95% CI 66-85% 95% CI 67-100% 95% CI 48-64% 95% CI 24-60% 95% CI 5-35% Number at risk by time Class 1 92 83 63 39 27 16 11 Strata Class 2 13 13 11 9 7 7 6 Class 3 189 153 102 66 47 33 24 Class 4 37 29 17 9 4 1 0 Class 5 30 15 4 3 1 1 1 0 12 24 36 48 60 72 Time (months) Hong et al. PLOS ONE. 2018.

Pooling early studies 1.00 +++ ++ + + + + + + + + + + + + ++ + ++ + + + + + + + ++ + + + + + + + + + + + + + + ++ + + + ++ + ++ + + + + All patients 0.75 + + + + + + + + + + + + + + + + + +++ + + + + + ++ + + + Overall survival + + + ++ + + + + + + ++ + + + + + + Strata Breast Other primary + + + + + + Class 1 + + + + + + + Kidney + + + + + ++ + + + Class 2 0.50 Prostate + + Class 3 + + + + + + + Class 4 + Time to metastasis Time to metastasis + ++ ++ + + + + Class 5 + +++ + ≥ 75 months < 75 months + + + + 0.25 # metastases ≤ 2 # metastases >2 + + Age ≤ 61 Age > 62 0.00 Class 1 Class 2 Class 3 Class 4 Class 5 n = 92 n = 13 n = 189 n = 37 n = 30 0 12 24 36 48 60 72 Time (months) 3-year OS 75% 3-year OS 85% 3-year OS 55% 3-year OS 38% 3-year OS 13% 95% CI 66-85% 95% CI 67-100% 95% CI 48-64% 95% CI 24-60% 95% CI 5-35% Number at risk by time Class 1 92 83 63 39 27 16 11 Strata Class 2 13 13 11 9 7 7 6 Class 3 189 153 102 66 47 33 24 Class 4 37 29 17 9 4 1 0 Class 5 30 15 4 3 1 1 1 0 12 24 36 48 60 72 Time (months) Hong et al. PLOS ONE. 2018.