Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Neurocognitive outcomes in a phase 3 randomised trial comparing adjuvant whole brain radiotherapy with observation after local treatment of brain metastases in patients with melanoma (#124)

Haryana Dhillon 1 , Gerald B Fogarty 2 3 , Kari Dolven-Jacobsen 4 , Rachael L Morton 2 5 , George Hruby 6 7 , Anna K Nowak 8 , Janette L Vardy 9 , Kate J Drummond 10 11 , Catherine Mandel 12 , Richard A Scolyer 2 13 , Brindha Shivalingam 14 , Mark R Middleton 15 , Bryan Burmeister 16 , Daniel E Roos 17 18 , Serigne N Lo 19 20 , Claudius H Reisse 4 , Elizabeth J Paton 1 21 , Narelle C Williams 1 22 , John F Thompson 2 23 , Angela Hong 2 3
  1. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  2. Melanoma Institute Australia, Sydney, NSW, Australia
  3. Mater Hospital, Sydney, NSW, Australia
  4. Oslo University Hospital, Oslo, Norway
  5. NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia
  6. Genesis Care, Sydney, NSW, Australia
  7. Royal North Shore Hospital, Sydney, NSW, Australia
  8. Medical School, University of Western Australia, Perth, WA, Australia
  9. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
  10. Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, Australia
  11. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia
  12. Swinburne University of Technology, Melbourne, VIC, Australia
  13. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  14. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  15. University of Oxford, Oxford, United Kingdom
  16. Genesis Care, Hervey Bay, QLD, Australia
  17. University of Adelaide, Adelaide, SA, Australia
  18. Royal Adelaide Hospital, Adelaide, SA, Australia
  19. Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
  20. Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  21. Australia and New Zealand Melanoma Trials Group, Sydney, NSW, Australia
  22. Australia and New Zealand Melanoma Trials Group, Sydney, NSW, Australia
  23. Department of melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Aims:

Concerns regarding neurocognitive function (NCF) after whole brain radiotherapy (WBRT) exist. This trial compared WBRT vs observation (OBS) following local treatment in patients with one to three melanoma brain metastases.  Here we present the NCF results.

 

Methods:

Objective NCF was evaluated in English speakers at baseline, then two-monthly.  Primary outcome was change in delayed recall at four months on the Hopkins Verbal Learning Test-Revised (HVLT-R).  Other NCF tests were also performed. A mixed linear model calculated the effect of intervention on relative raw scores, adjusted for baseline score and time. Cognitive failure was determined by Reliable Change Index; global cognitive impairment was defined as Global Deficit Score >0.5. Analysis was by intention-to-treat, with nominal two-sided significance level 5%.

 

Results:

207 patients were randomised (100 WBRT, 107 OBS) from 31 sites in 3 countries. NCF testing was completed by 73 WBRT and 70 OBS patients at baseline. Patients had similar characteristics.

 

OBS group had greater relative improvement in HVLT-R from baseline at every timepoint. At four months, delayed recall declined 2.7% from baseline in WBRT but improved by 20.9% in OBS; overall adjusted average intervention effect 23.6% (95%CI 9.0-38.2%; p=0.0018).  Significant effects were seen between groups at four months in HVLT-total recall and delayed recognition, the overall adjusted average intervention effects were 8.3% (95%CI 0.4-16.1%; p=0.0397) and 25.0% (95%CI 14.3-35.7%; p<0.0001) respectively.  There were no significant differences in time to cognitive failure (log-rank p=0.44), or proportions with global cognitive impairment at four months (OBS 32% vs WBRT 53%; p=0.11). Cognitive decline in T-scores, baseline to four months, of 1SD in at least one NCF test occurred in 24/38 (63%) WBRT vs 11/25 (44%) OBS (p=0.13).

 

Conclusion:


Cognitive impairment was common in both groups but greater memory decline occurred in patients receiving WBRT.