Hippocampus Avoidance PCI vs PCI

Study Overview
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Brief Summary
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Using Intensity Modulated radiotherapy it is possible to treat the entire brain to standard dosages of whole-brain radiation, while keeping the radiation dose to the hippocampus low. However, a clear relationship between radiation dose and damage to the hippocampal stem cells has not been established yet. This study is initiated to investigate the early and delayed neurotoxicity of PCI and to assess in a randomised design the benefits and risks of sparing the hippocampus in Small Cell Lung Cancer patients who receive PCI.

Official Title
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Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance in SCLC a Randomized Phase III Trial

Conditions
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Small Cell Lung Cancer, Lung Cancer

Intervention / Treatment
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* Radiation: Radiation Prophylactic Cranial Irradiation
* Radiation: Radiation Hippocampal Avoidance PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Small Cell Lung Cancer patients (stage I-III or stage IV without clinical or radiological evidence of brain metastases) candidate for PCI, i.e. without progressive disease after chemo-radiotherapy in stage I-III or after a remission after chemotherapy in stage IV Sufficient proficiency in Dutch Exclusion Criteria: Prior radiotherapy to the brain Clinical evidence for brain metastases or primary brain tumors- Evidence of progressive extracranial metastatic disease Previous malignancy < 2 years ago except for adequately treated basal cell carcinoma of the skin and carcinoma in situ of the cervix Any systemic anticancer treatment during PCI or within 3 weeks before start PCI Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prophylactic Cranial Irradiation<br>Radiation. Prophylactic Cranial Irradiation: 10 times 2.5 Gy (total 25 Gy) | Radiation: Radiation Prophylactic Cranial Irradiation<br> <br> |
| Experimental: Hippocampal Avoidance PCI<br>Radiation. Hippocampal Avoidance PCI. 10 times 2.5 Gy (total 25 Gy). | Radiation: Radiation Hippocampal Avoidance PCI<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neurocognitive decline | Each patient's total recall score recorded at 4 months will be compared to baseline and dichotomized into success (decline less or equal 5 points) or failure (decline more than 5 points). The difference between the groups, in terms of dichotomized decline will be tested by means of the Fisher's exact test. A p-value less than 0.049 will be considered significant. The primary analysis will be based on an intention-to-treat principle. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety | Brain metastases Time from randomization to the occurrence of brain metastases will be calculated and depicted in a cumulative incidence plot. Sensitivity analysis will be performed to assess the value of PCI vs HA-PCI treatment once considering patients dying without distant brain metastases to be censored and once using competing risk analysis considering distant metastases and death as separate events | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hippocampal Avoidance Prophylactic Cranial Irradiation, Prophylactic Cranial Irradiation