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Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation

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Abstract

Background

Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) techniques have been developed to reduce radiation damage to the hippocampus. An inter-observer hippocampus delineation analysis was performed and the influence of the delineation variability on dose to the hippocampus was studied.

Materials and methods

For five patients, seven observers delineated both hippocampi on brain MRI. The intra-class correlation (ICC) with absolute agreement and the generalized conformity index (CIgen) were computed. Median surfaces over all observers’ delineations were created for each patient and regional outlining differences were analysed. HA-PCI dose plans were made from the median surfaces and we investigated whether dose constraints in the hippocampus could be met for all delineations.

Results

The ICC for the left and right hippocampus was 0.56 and 0.69, respectively, while the CIgen ranged from 0.55 to 0.70. The posterior and anterior-medial hippocampal regions had most variation with SDs ranging from approximately 1 to 2.5 mm. The mean dose (Dmean) constraint was met for all delineations, but for the dose received by 1% of the hippocampal volume (D1%) violations were observed.

Conclusion

The relatively low ICC and CIgen indicate that delineation variability among observers for both left and right hippocampus was large. The posterior and anterior-medial border have the largest delineation inaccuracy. The hippocampus Dmean constraint was not violated.

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References

  1. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.

    Article  PubMed  Google Scholar 

  2. Gondi V, Tomé WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol. 2010;97:370–6.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Le Péchoux C, Sun A, Slotman BJ, De Ruysscher D, Belderbos J, Gore EM. Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol. 2016;17:e277–93.

    Article  Google Scholar 

  4. Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341:476–84.

    Article  PubMed  Google Scholar 

  5. Slotman B, Faivre-Finn C. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357:664–72.

    Article  CAS  PubMed  Google Scholar 

  6. Wolfson AH, Bae K, Komaki R, Meyers C, Movsas B, Le Pechoux C, et al. Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease. Int J Radiat Oncol Biol Phys. 2011;81:77–84.

    Article  PubMed  Google Scholar 

  7. Gondi V, Paulus R, Bruner DW, Meyers CA, Gore EM, Wolfson A, et al. Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214. Int J Radiat Oncol Biol Phys. 2013;86:656–64.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Le Péchoux C, Laplanche A, Faivre-Finn C, Ciuleanu T, Wanders R, Lerouge D, et al. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol. 2011;22:1154–63.

    Article  PubMed  Google Scholar 

  9. Slotman BJ, Mauer ME, Bottomley A, Faivre-Finn C, Kramer GWPM, Rankin EM, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol. 2009;27:78–84.

    Article  PubMed  Google Scholar 

  10. Groen HJM, Dingemans A-MC, Belderbos J, Tissing-Tan C, Herder G, Haitjema T, et al. Prophylactic cranial irradiation (PCI) versus observation in radically treated stage III non-small cell lung cancer (NSCLC): a randomized phase III NVALT11 study. J Clin Oncol. 2017. https://doi.org/10.1200/jco.2017.35.15_suppl.8502.

    Article  PubMed  Google Scholar 

  11. Burgess N, Maguire EA, O’Keefe J. The human hippocampus and spatial and episodic memory. Neuron. 2002;35:625–41.

    Article  CAS  PubMed  Google Scholar 

  12. Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010;11:339–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ferrer I, Serrano T, Alcantara S, Tortosa A, Graus F. X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis. J Neuropathol Exp Neurol. 1993;52:370–8.

    Article  CAS  PubMed  Google Scholar 

  14. Raber J, Rola R, LeFevour A, Morhardt D, Curley J, Mizumatsu S, et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res. 2004;162:39–47.

    Article  CAS  PubMed  Google Scholar 

  15. Nagai R, Tsunoda S, Hori Y, Asada H. Selective vulnerability to radiation in the hippocampal dentate granule cells. Surg Neurol. 2000;53:503–6 (discussion 506–7).

    Article  CAS  PubMed  Google Scholar 

  16. Madsen TM, Kristjansen PEG, Bolwig TG, Wörtwein G. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience. 2003;119:635–42.

    Article  CAS  PubMed  Google Scholar 

  17. Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003;63:4021–7.

    CAS  PubMed  Google Scholar 

  18. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. 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;32:3810–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, et al. 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;78:1244–52.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ghia A, Tomé WA, Thomas S, Cannon G, Khuntia D, Kuo JS, et al. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007;68:971–7.

    Article  PubMed  Google Scholar 

  21. Gondi V, Tome WA, Marsh J, Struck A, Ghia A, Turian JV, et al. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933. Radiother Oncol. 2010;95:327–31.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kundapur V, Ellchuk T, Ahmed S, Gondi V. Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation. Radiat Oncol Biol. 2015;91:781–6.

    Article  Google Scholar 

  23. Van Kesteren Z, Olszewska A, Belderbos J, Van Vliet-Vroegindeweij C. The distribution of brain metastases in the perihippocampal region (Regarding Gondi et al., Radiother Oncol 2010;95:327–331). Radiother Oncol. 2011;98:144.

    Article  Google Scholar 

  24. Redmond KJ, Hales RK, Anderson-Keightly H, Zhou XC, Kummerlowe M, Sair HI, et al. Prospective study of hippocampal-sparing prophylactic cranial irradiation in limited-stage small cell lung cancer. Int J Radiat Oncol Biol Phys. 2017;98:603–11.

    Article  PubMed  Google Scholar 

  25. Duchesne S, Valdivia F, Robitaille N, Mouiha A, Valdivia FA, Bocchetta M, et al. Manual segmentation qualification platform for the EADC-ADNI harmonized protocol for hippocampal segmentation project. Alzheimer’s Dement. 2015;11:161–74.

    Article  Google Scholar 

  26. Hsu F, Carolan H, Nichol A, Cao F, Nuraney N, Lee R, et al. Whole brain radiotherapy with hippocampal avoidance and simultaneous integrated boost for 1–3 brain metastases: a feasibility study using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys. 2010;76:1480–5.

    Article  PubMed  Google Scholar 

  27. Gutiérrez AN, Westerly DC, Tomé WA, Jaradat HA, Mackie TR, Bentzen SM, et al. Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys. 2007;69:589–97.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002;33:341–55.

    Article  CAS  PubMed  Google Scholar 

  29. Gondi V, Tome WA, Rowley HA, Mehta MP. Hippocampal Contouring: A Contouring Atlas for RTOG 0933 n.d. https://www.rtog.org/CoreLab/ContouringAtlases/HippocampalSparing.aspx. Accessed 25 Sept 2017).

  30. Jack CR, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, et al. The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods. J Magn Reson Imaging. 2008;27:685–91.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wolthaus JWH, van Herk M, Muller SH, Belderbos JSA, Lebesque JV, de Bois JA, et al. Fusion of respiration-correlated PET and CT scans: correlated lung tumour motion in anatomical and functional scans. Phys Med Biol. 2005;50:1569–83.

    Article  CAS  PubMed  Google Scholar 

  32. Kouwenhoven E, Giezen M, Struikmans H. Measuring the similarity of target volume delineations independent of the number of observers. Phys Med Biol. 2009;54:2863–73.

    Article  PubMed  Google Scholar 

  33. Bartel F, Vrenken H, Bijma F, Barkhof F, Van Herk M, De Munck JC. Regional analysis of volumes and reproducibilities of automatic and manual hippocampal segmentations. PLoS ONE. 2017;12:e0166785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Steenbakkers RJHM, Duppen JC, Fitton I, Deurloo KEI, Zijp LJ, Comans EFI, et al. Reduction of observer variation using matched CT-PET for lung cancer delineation: a three-dimensional analysis. Int J Radiat Oncol Biol Phys. 2006;64:435–48.

    Article  PubMed  Google Scholar 

  35. Diwanji T, Snider JW, Koroulakis A, Feigenberg SJ, Mohindra P, Kwok Y, et al. Interobserver variability in atlas-based, manual segmentation of the hippocampus in patients with brain metastases. Int J Radiat Oncol Biol Phys. 2016;96:E130.

    Article  Google Scholar 

  36. Barnes J, Foster J, Boyes RG, Pepple T, Moore EK, Schott JM, et al. A comparison of methods for the automated calculation of volumes and atrophy rates in the hippocampus. Neuroimage. 2008;40:1655–71.

    Article  CAS  PubMed  Google Scholar 

  37. Basso M, Yang J, Warren L, MacAvoy MG, Varma P, Bronen RA, et al. Volumetry of amygdala and hippocampus and memory performance in Alzheimer’s disease. Psychiatry Res Neuroimaging. 2006;146:251–61.

    Article  Google Scholar 

  38. Jack CR Jr, Slomkowski M, Gracon S, Hoover TM, Felmlee JP, et al. MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD. Neurology. 2003;60:253.

    Article  PubMed  Google Scholar 

  39. Wenger E, Mårtensson J, Noack H, Bodammer NC, Kühn S, Schaefer S, et al. Comparing manual and automatic segmentation of hippocampal volumes: reliability and validity issues in younger and older brains. Hum Brain Mapp. 2014;35:4236–48.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Boccardi M, Ganzola R, Bocchetta M, Pievani M, Redolfi A, Bartzokis G, et al. Survey of protocols for the manual segmentation of the hippocampus: preparatory steps towards a joint EADC-ADNI harmonized protocol. Adv Alzheimer’s Dis. 2011;2:111–25.

    Google Scholar 

  41. Dill V, Franco AR, Pinho MS. Automated methods for hippocampus segmentation: the evolution and a review of the state of the art. Neuroinformatics. 2015;13:133–50.

    Article  PubMed  Google Scholar 

  42. Di Biase S, Trignani M, Caravatta L, Voicu PI, Di Carlo C, Vinciguerra A, et al. Development of a contouring guide in three different head set-ups for hippocampal sparing radiotherapy: a practical approach. Radiol Med. 2017;122:683–9.

    Article  PubMed  Google Scholar 

  43. Carmichael OT, Aizenstein HA, Davis SW, Becker JT, Thompson PM, Meltzer CC, et al. Atlas-based hippocampus segmentation in Alzheimer’s disease and mild cognitive impairment. Neuroimage. 2005;27:979–90.

    Article  PubMed  Google Scholar 

  44. Kindts I, Vandermeulen A, Verhoeven K, Laenen A, Hortobágyi E, Weltens CG. A central review platform improves the quality of regional lymph node delineation for breast cancer radiation therapy. Int J Radiat Oncol. 2016;96:E38–9.

    Article  Google Scholar 

  45. Joye I, Lambrecht M, Jegou D, Hortobágyi E, Scalliet P, Haustermans K. Does a central review platform improve the quality of radiotherapy for rectal cancer? Results of a national quality assurance project. Radiother Oncol. 2014;111:400–5.

    Article  PubMed  Google Scholar 

  46. Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 2011;56:907–22.

    Article  PubMed  Google Scholar 

  47. Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012;61:1402–18.

    Article  PubMed  Google Scholar 

  48. Morey RA, Petty CM, Xu Y, Pannu Hayes J, Wagner HR, Lewis DV, et al. A comparison of automated segmentation and manual tracing for quantifying hippocampal and amygdala volumes. Neuroimage. 2009;45:855–66.

    Article  PubMed  Google Scholar 

  49. Morey RA, Selgrade ES, Wagner HR, Huettel SA, Wang L, McCarthy G. Scan-rescan reliability of subcortical brain volumes derived from automated segmentation. Hum Brain Mapp. 2010;31:1751–62.

    PubMed  PubMed Central  Google Scholar 

  50. Pardoe HR, Pell GS, Abbott DF, Jackson GD. Hippocampal volume assessment in temporal lobe epilepsy: how good is automated segmentation? Epilepsia. 2009;50:2586–92.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Doring TM, Kubo TTA, Cruz LCH, Juruena MF, Fainberg J, Domingues RC, et al. Evaluation of hippocampal volume based on MR imaging in patients with bipolar affective disorder applying manual and automatic segmentation techniques. J Magn Reson Imaging. 2011;33:565–72.

    Article  PubMed  Google Scholar 

  52. Mulder ER, de Jong RA, Knol DL, van Schijndel RA, Cover KS, Visser PJ, et al. Hippocampal volume change measurement: quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST. Neuroimage. 2014;92:169–81.

    Article  PubMed  Google Scholar 

  53. Wang H, Suh JW, Das SR, Pluta JB, Craige C, Yushkevich PA. Multi-atlas segmentation with joint label fusion. IEEE Trans Pattern Anal Mach Intell. 2013;35:611–23.

    Article  PubMed  Google Scholar 

  54. Zhu H, Cheng H, Yang X, Fan Y. Alzheimer’s disease neuroimaging initiative. metric learning for multi-atlas based segmentation of hippocampus. Neuroinformatics. 2017;15:41–50.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank C. Chun for her previous work and contribution to this study. This study was funded by ZonMW (Grand Number: 104002006), the Netherlands organisation for health research and development, the Dutch Cancer Society (KWF, Grand Number: 2013-6096) and Netherlands Cancer Institute (NKI) in Amsterdam. We would also like to acknowledge the government agency for Innovation by Science and Technology (A13/TT/1503—IWT/TBM) and NutsOhra (Project 100 3-105).

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Correspondence to J. Belderbos.

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Bartel, F., van Herk, M., Vrenken, H. et al. Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation. Clin Transl Oncol 21, 178–186 (2019). https://doi.org/10.1007/s12094-018-1903-7

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