Biomedical papers - Ahead of Print

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | 10.5507/bp.2017.031

Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study

Tomas Kazdaa,b, Miroslav Vrzala,b, Tomas Prochazkaa,b, Petr Dvoraceka,b, Petr Burkona,b, Petr Pospisila,b, Adam Dziackyc, Tomas Nikla,b, Radim Jancalekd,e, Pavel Slampaa,b,h, Radek Lakomyf,g
a Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
b Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic
c Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
d Department of Neurosurgery, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
e Department of Neurosurgery, St. Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic
f Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
g Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic
h Regional Center for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic

Aims: Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans.

Methods: HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH").

Results: All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100 % was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2 % (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2 % (P=0.005) and 10.9 % (P=0.005) respectively.

Conclusions: LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

Keywords: brain metastases, hippocampus, memory, cognition, HA WBRT

Received: May 12, 2017; Accepted: June 20, 2017; Prepublished online: July 20, 2017


References

  1. Gondi V, Tomé WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol 2010;97(3):370-6. Go to original source... Go to PubMed...
  2. Kazda T, Jancalek R, Pospisil P, Sevela O, Prochazka T, Vrzal M, Burkon P, Slavik M, Hynkova L, Slampa P, Laack NN. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol 2014;9:139. Go to original source... Go to PubMed...
  3. Awad R, Fogarty G, Hong A, Kelly P, Ng D, Santos D, Haydu L. Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases - the first Australian experience. Radiat Oncol 2013;8:62. Go to original source... Go to PubMed...
  4. Marsh JC, Godbole R, Diaz AZ, Gielda BT, Turian JV. Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: a dosimetric feasibility study. J Med Imaging Radiat Oncol 2011;55(4):442-9. Go to original source... Go to PubMed...
  5. Marsh JC, Ziel GE, Diaz AZ, Wendt JA, Gobole R, Turian JV. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment. J Med Imaging Radiat Oncol 2013;57(3):378-83. Go to original source... Go to PubMed...
  6. Kazda T, Pospíšil P, Doleželová H, Jančálek R, Slampa P. Whole brain radiotherapy: Consequences for personalized medicine. Rep Pract Oncol Radiother 2013;18(3):133-8. Go to original source... Go to PubMed...
  7. Lee TM, Yip JT, Jones-Gotman M. Memory deficits after resection from left or right anterior temporal lobe in humans: A meta-analytic review. Epilepsia 2002;43(3):283-91. Go to original source... Go to PubMed...
  8. Jalali R, Mallick I, Dutta D, Goswami S, Gupta T, Munshi A, Deshpande D, Sarin R. Factors influencing neurocognitive outcomes in young patients with benign and low-grade brain tumors treated with stereotactic conformal radiotherapy. Int J Radiat Oncol Biol Phys 2010;77(4):974-9. Go to original source... Go to PubMed...
  9. Farjam R, Pramanik P, Aryal MP, Srinivasan A, Chapman CH, Tsien CI, Lawrence TS, Cao Y. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction. Int J Radiat Oncol 2015;93(4):908-15. Go to original source...
  10. Pospisil P, Kazda T, Bulik M, Dobiaskova M, Burkon P, Hynkova L, Slampa P, Jancalek R. Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences. Radiat Oncol 2015;10:211. Go to original source... Go to PubMed...
  11. Pospisil P, Kazda T, Hynkova L, Bulik M, Dobiaskova M, Burkon P, Laack NN, Slampa P, Jancalek R. Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study. Radiother Oncol 2017;122(3):373-9. Go to original source... Go to PubMed...
  12. Gondi V, Hermann BP, Mehta MP, Tomé WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 2013;85(2):348-54. Go to original source... Go to PubMed...
  13. Gondi V, Pugh SL, Tomé WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933): A Phase II Multi-Institutional Trial. J Clin Oncol 2014;32(34):3810-6. Go to original source... Go to PubMed...
  14. Hippocampal contouring: a contouring Atlas for RTOG 0933. Available from: [http://www.rtog.org/LinkClick.aspx?fileticket=59vaU8vfgQc%3d&tabid=338]
  15. Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, Khuntia D, Tomé WA. Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2010;78(4):1244-52. Go to original source... Go to PubMed...
  16. Scoccianti S, Detti B, Gadda D, Greto D, Furfaro I, Meacci F, Simontacchi G, Di Brina L, Bonomo P, Giacomelli I, Meattini I, Mangoni M, Cappelli S, Cassani S, Talamonti C, Bordi L, Livi L. Organs at risk in the brain and their dose-constraints in adults and in children: A radiation oncologist's guide for delineation in everyday practice. Radiother Oncol 2015;114(2):230-8. Go to original source... Go to PubMed...
  17. Bolsi A, Fogliata A, Cozzi L. Radiotherapy of small intracranial tumours with different advanced techniques using photon and proton beams: a treatment planning study. Radiother Oncol 2003;68(1):1-14. Go to original source... Go to PubMed...
  18. Connor M, Karunamuni R, McDonald C, White N, Pettersson N, Moiseenko V, Seibert T, Marshall D, Cervino L, Bartsch H, Kuperman J, Murzin V, Krishnan A, Farid N, Dale A, Hattangadi-Gluth J. Dose-dependent white matter damage after brain radiotherapy. Radiother Oncol 2016;121(2):209-16. Go to original source... Go to PubMed...
  19. Karunamuni R, Bartsch H, White NS, Moiseenko V, Carmona R, Marshall DC, Seibert TM, McDonald CR, Farid N, Krishnan A, Kuperman J, Mell L, Brewer JB, Dale AM, Hattangadi-Gluth JA.. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma. Int J Radiat Oncol Biol Phys 2016;94(2):297-304. Go to original source... Go to PubMed...
  20. Seibert TM, Karunamuni R, Bartsch H, Kaifi S, Krishnan AP, Dalia Y, Burkeen J, Murzin V, Moiseenko V, Kuperman J, White NS, Brewer JB, Farid N, McDonald CR, Hattangadi-Gluth JA. Radiation Dose - Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging. Int J Radiat Oncol 2017;97(2):263-9. Go to original source...
  21. Balentova S, Hajtmanova E, Filova B, Borbelyova V, Lehotsky J. Effect of Fractionated Irradiation on the Hippocampus in an Experimental Model. Klin Onkol 2015;28(3):191-9. Go to original source... Go to PubMed...
  22. Tomé WA, Gökhan Ş, Gulinello ME, Brodin NP, Heard J, Mehler MF, Guha C. Hippocampal-dependent neurocognitive impairment following cranial irradiation observed in pre-clinical models: current knowledge and possible future directions. Br J Radiol. 2016;89(1057):20150762. Go to original source... Go to PubMed...
  23. Lakomy R, Hynkova L, Pospisil P, Burkon P, Slavik M, Slampa P, Jancalek R, Kazda T. Patterns of failure after brain metastases radiotherapy: reflections on the importance for treatment and clinical trials reporting. Neoplasma 2017 Mar 3. [Epub ahead of print] doi: 10.4149/neo_2017_302 Go to original source... Go to PubMed...
  24. Fogarty GB, Hong A, Gondi V, Burmeister B, Jacobsen K, Lo S, Paton E, Shivalingam B, Thompson JF. Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice. BMC Cancer 2016; 16:372. Go to original source... Go to PubMed...
  25. Mehta MP, Aoyama H, Gondi V. The Changing Role of Whole-Brain Radiotherapy: Demise or Time for Selective Usage? JAMA Oncol 2017 Jan 5 [Epub ahead of print] doi: 10.1001/jamaoncol.2016.5414 Go to original source...
  26. Matzenauer M, Vrana D, Vlachova Z, Cwiertka K, Kalita O, Melichar B. Radiotherapy management of brain metastases using conventional linear accelerator. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016;160(3):412-6. Go to original source... Go to PubMed...
  27. Soltys SG, Kirkpatrick JP, Laack NN, Kavanagh BD, Breneman JC, Shih HA. Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases. Int J Radiat Oncol 2015;92(5):963-6. Go to original source...