Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases

Abstract

Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.

Retrospective analysis of dosimetry on hippocampal-avoidance whole-brain radiotherapy in a regional hospital

“…Following these prospective clinical trials to confer neuro-cognitive protection in metastatic brain disease, HA-WBRT has gained clinical acceptance (7,8). However, perihippocampal failure has been reported from clinical observations (18)(19)(20). We have also reported unusual cases of intracranial failure following HA-WBRT therapy and perihippocampal failure rate was about 8% in…”

“…our previous report (18). RTOG 0933 recommended stringent dose criteria which required a high dose homogeneity and precise radiation delivery.…”

Perihippocampal failure after hippocampal-avoidance brain radiotherapy in small cell lung cancer patients: Cases report and literature review

“…Hippocampal contouring and HA-WBRT planning directives of 3 cases were guided by the RTOG 0933 criteria, [10] and the technique and clinical study are described in our previous study. [14,15] To investigate whether a deviation of underdose in the HA region led to perihippocampal failure, we assessed the parameters of dosimetry in the HA-WBRT planning of our cases (Table 1). We compared the brain dose of patients A to C and the underdose region around the HA region by maping the MRI scans of intracranial failure and previous planning CT scan of simulation and found that a deviation of the underdosed region within the perihippocampal failure was approximately 55% to 63%.…”