1 Treatment of Brain Metastases An Overview and Pending Research Questions To Answer Olav E. Yri, MD, PhD www.ntnu.no/prc European Palliative Care Research Centre (PRC)
The brain metastases diagnosis
Outline Incidence Classification Clinical trials Treatment options based on clinical trials Pending questions to answer
What do we know about the incidence of brain metastases?
Neurosurg Clin N Am 22 (2011) 1-6
Incidence rate in Sweden 1987-2006
Can we predict the prognosis?
Classification systems J.D. Zindler et al. / Radiotherapy and Oncology 106 (2013) 370 374
DS-GPA median survival times Breast cancer Lung cancer
Clinical trials vs. Real life Worst Class 14% 15% Best Class 20% 20% Best 4% 1 2 3 Worst 51% Intermediate 45% 66% Intermediate class 66% P.M. Mulvenna / Clinical Oncology 22 (2010) 365 373
Clinical trials on treatment
Treatment options Surgical resection Radiotherapy Whole brain radiotherapy (WBRT) Stereotactic radiosurgery (SRS) Systemic treatments Chemotherapy Targeted therapies Immunotherapy Steroids
17 randomized clinical trials on treatment No of mets Treatments No of patients Horton 1971 any Steroids/WBRT 48 Patchell 1990 1 S/WBRT 48 Vecht 1993 1 S/WBRT 63 Mintz 1996 1 S/WBRT 84 Patchell 1998 1 S/WBRT, OBS 95 Roos 2006 1 SRS, S/WBRT,OBS 19 Muacevic 2008 1 SRS/WBRT 64 Kepka 2016 1 S/WBRT,SRS 59 Kondziolka 1999 2-4 WBRT/SRS 27 Andrews 2004 1-3 WBRT/SRS 333 Chang 2009 1-3 SRS/WBRT,OBS 58 Kocher 2011 1-3 SRS,S/WBRT,OBS 359 Mahajan 2017 1-3 S,SRS/OBS 132 Aoyama 2006 1-4 SRS/WBRT,OBS 132 Brown 2016 1-4 SRS/WBRT,OBS 213 Brown 2017 1-4 S/SRS,WBRT 194 Mulvenna 2016 any Steroids/WBRT 538 n=1880
The first of only two randomized trials on whole brain radiotherapy
QUARTZ Trial The second study (2016) Overall survival
Treatment options based on clinical trials
Local progression/control http://www.aboutcancer.com/gk_brain_mets.htm
Distal progression/control http://cancergrace.org/lung/2007/04/18/xcytrin-for-nsclc-brain-mets/
Intracranial progression/control +
Patients with 1-4 lesions Surgical resection of solitary lesions may improve overall survival Postoperative SRS improves local progression rates of treated lesions compared to observation Both SRS and WBRT improves local progression rates of treated lesions but only WBRT improves distal progression rates Combining WBRT and SRS improves intracranial progression rates
Patients with 1-4 lesions Treatment with WBRT, SRS or combination no difference in overall survival WBRT may be associated with cognitive decline and reduced quality of life compared to SRS Many advocate SRS and active surveillance with salvage therapy if progression
Patients with multiple (>4) lesions Few clinical trials Some evidence for SRS for more than four lesions Retrospective/observational studies No randomized clinical trials reported yet Is WBRT the golden standard?
Summary on brain metastases Incidence believed to be increasing Classification systems may predict prognosis But based on selected patient material Few studies on patients with more than four lesions New systemic treatments become more important Several issues are either unanswered or need more research to be answered properly
Pending questions to answer
Pending questions to answer What is the «real life» incidence of brain metastases? Are prognostic parametres from clinical trials valid for «real life patients»? What are clinically relevant indications for treatment? How does WBRT really affect cognitive function and quality of life?
Pending questions to answer Can cognitive side effects of WBRT be reduced? What is the role of novel systemic treatments? Total number or volume of metastatic lesions more important for SRS? Can SRS replace surgical resection for solitary lesions?
Pending questions to answer What is the optimal treatment for patients with multiple metastases and good performance status? WBRT? SRS? The role of systemic treatments?
Pending questions to answer What should be standards in future clinical trials Patient selection criteria Radiological end-points Clinical end-points QoL-measurement and dimensions Clinical trials hard to perform Physician/patient bias toward specific treatments Poor patient recruitment
Brain Metastases in Norway a comprehensive research project WP1: Olav E Yri Phd. MD WP4: Marianne L Smebye Phd. MD
Thank you http://oncolex.org/