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Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.
Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.
Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.
Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved.
Trial registration: Retrospectively registered.
Keywords
hippocampus, volume, dose effect, glioblastoma
This is a list of supplementary files associated with this preprint. Click to download.
- Hippocampusannex1RO.docx
Annex 1: Relevant comparison of volumes according to MRI • Annex 1a: Comparison of volumes measured on MRI • Annex 1b: Comparison between changes in volume during the intervals between MRIs • Annex 1c: Comparison between changes in percent volume during the intervals between MRIs
- Hippocampusannex2RO.docx
Annex 2: Relevant comparison of hippocampal volumes their changes according to the time of the MRIs • Annex 2a: Comparison between volumes at a given MRI time according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2b: Comparison between volumes measured on different MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2c: Comparison between changes in volumes during the interval between MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2d: Comparison between changes in % volumes during interval between MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy
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CURRENT STATUS: Under Review
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Posted 27 Apr, 2021
Editorial decision: Major revision
On 27 Apr, 2021
Review #2 received
Received 26 Apr, 2021
Reviewer #2 agreed
On 11 Apr, 2021
Review #1 received
Received 07 Apr, 2021
Reviewer #1 agreed
On 05 Apr, 2021
Reviews received
Received 05 Apr, 2021
Reviewers invited
Invitations sent on 04 Apr, 2021
First submitted
On 04 Apr, 2021
Editor assigned
On 03 Apr, 2021
Submission checks complete
On 03 Apr, 2021
Editor invited
On 03 Apr, 2021
This version was not preprinted
Version 1
Posted 06 Apr, 2021
No community comments so far
Reviewer #1 agreed
On 05 Apr, 2021
Reviewers invited
Invitations sent on 04 Apr, 2021
Editor assigned
On 03 Apr, 2021
Submission checks complete
On 03 Apr, 2021
Editor invited
On 03 Apr, 2021
First submitted
On 25 Mar, 2021
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This preprint is under consideration at Radiation Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 27 Apr, 2021
Editorial decision: Major revision
On 27 Apr, 2021
Review #2 received
Received 26 Apr, 2021
Reviewer #2 agreed
On 11 Apr, 2021
Review #1 received
Received 07 Apr, 2021
Reviewer #1 agreed
On 05 Apr, 2021
Reviews received
Received 05 Apr, 2021
Reviewers invited
Invitations sent on 04 Apr, 2021
First submitted
On 04 Apr, 2021
Editor assigned
On 03 Apr, 2021
Submission checks complete
On 03 Apr, 2021
Editor invited
On 03 Apr, 2021
This version was not preprinted
Version 1
Posted 06 Apr, 2021
No community comments so far
Reviewer #1 agreed
On 05 Apr, 2021
Reviewers invited
Invitations sent on 04 Apr, 2021
Editor assigned
On 03 Apr, 2021
Submission checks complete
On 03 Apr, 2021
Editor invited
On 03 Apr, 2021
First submitted
On 25 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.
Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.
Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.
Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved.
Trial registration: Retrospectively registered.
This is a list of supplementary files associated with this preprint. Click to download.
- Hippocampusannex1RO.docx
Annex 1: Relevant comparison of volumes according to MRI • Annex 1a: Comparison of volumes measured on MRI • Annex 1b: Comparison between changes in volume during the intervals between MRIs • Annex 1c: Comparison between changes in percent volume during the intervals between MRIs
- Hippocampusannex2RO.docx
Annex 2: Relevant comparison of hippocampal volumes their changes according to the time of the MRIs • Annex 2a: Comparison between volumes at a given MRI time according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2b: Comparison between volumes measured on different MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2c: Comparison between changes in volumes during the interval between MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy • Annex 2d: Comparison between changes in % volumes during interval between MRIs and according to subgroup: In group 1 (G1: n=6), in both hippocampi, the D40% was < 7.4 Gy; in group 2 (G2: n=13), the Hcontra D40% was < 7.4 Gy; and in group 3 (G3: n=30), the D40% for both hippocampi was > 7.4 Gy
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