Temporal lobe necrosis in head and neck cancer patients after proton therapy to the skull base Journal Article


Authors: Kitpanit, S.; Lee, A.; Pitter, K. L.; Fan, D.; Chow, J. C. H.; Neal, B.; Han, Z.; Fox, P.; Sine, K.; Mah, D.; Dunn, L. A.; Sherman, E. J.; Michel, L.; Ganly, I.; Wong, R. J.; Boyle, J. O.; Cohen, M. A.; Singh, B.; Brennan, C. W.; Gavrilovic, I. T.; Hatzoglou, V.; O’Malley, B.; Zakeri, K.; Yu, Y.; Chen, L.; Gelblum, D. Y.; Kang, J. J.; McBride, S. M.; Tsai, C. J.; Riaz, N.; Lee, N. Y.
Article Title: Temporal lobe necrosis in head and neck cancer patients after proton therapy to the skull base
Abstract: Purpose: To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods: Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters. Results: Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion: The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy. Copyright 2020 The Author(s)
Keywords: head and neck cancer; toxicity; proton therapy; temporal lobe necrosis
Journal Title: International Journal of Particle Therapy
Volume: 6
Issue: 4
ISSN: 2331-5180
Publisher: Particle Therapy Cooperative Group  
Date Published: 2021-01-01
Start Page: 17
End Page: 28
Language: English
DOI: 10.14338/ijpt-20-00014.1
PROVIDER: scopus
PMCID: PMC7302730
PUBMED: 32582816
DOI/URL:
Notes: Article -- The issue publication date is Spring 2020 -- Export Date: 1 December 2021 -- Source: Scopus
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MSK Authors
  1. Daphna Y Gelblum
    227 Gelblum
  2. Jay O Boyle
    148 Boyle
  3. Bhuvanesh Singh
    242 Singh
  4. Loren Michel
    61 Michel
  5. Eric J Sherman
    339 Sherman
  6. Cameron Brennan
    225 Brennan
  7. Nadeem Riaz
    414 Riaz
  8. Nancy Y. Lee
    870 Lee
  9. Richard J Wong
    411 Wong
  10. Ian Ganly
    429 Ganly
  11. Ken L Pitter
    53 Pitter
  12. Sean Matthew McBride
    293 McBride
  13. Lara   Dunn
    141 Dunn
  14. Chiaojung Jillian   Tsai
    238 Tsai
  15. Marc A Cohen
    130 Cohen
  16. Anna Lee
    45 Lee
  17. Dan Fan
    16 Fan
  18. Yao Yu
    112 Yu
  19. Jung Yun Kang
    49 Kang
  20. Linda Chang Chen
    67 Chen
  21. Kaveh Zakeri
    81 Zakeri