Hippocampal-Sparing Prophylactic Cranial Irradiation in Pathologically Nodal Positive Non-Small-Cell Lung Cancer

NCT ID: NCT02448992

Last Updated: 2023-05-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-01
• Study Completion Date: 2026-12-31

Brief Summary

Background. During the clinical course of patients with locoregionally advanced non-small-cell lung cancer (LA-NSCLC) who have undergone aggressive treatment, brain metastasis (BM) is a frequent seen pattern of disease relapse, which cannot be ignored. It still remains unresolved whether prophylactic cranial irradiation (PCI) via whole brain radiotherapy (WBRT) should be recommended for NSCLC patients with stage III or pathologically nodal positive disease. Actually, PCI would significantly decrease the incidence of BM; however, potential WBRT-related neurocognitive function (NCF) sequelae are indeed a concern, which has made PCI seldom applied in clinical practice. In terms of the time course of WBRT-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline principally involve impairments of episodic memory, which has been significantly associated with functions of the hippocampus. This study thus aims to explore the impact of PCI on the subsequent risk of developing BM and the multi-domain neurobehavioral functions in our eligible patients.

Methods. Potentially eligible subjects are postoperative NSCLC patients with a status of pathologically nodal metastasis (pN+). Patients randomly assigned to the PCI arm will undergo the course of hippocampal-sparing PCI after they complete the fourth course of adjuvant platinum-based chemotherapy. Radiotherapy dose will be 3000 cGy in 15 fractions during three weeks. Except for the administration of hippocampal-sparing PCI, patients assigned to the observation arm should receive the same baseline and follow-up brain imaging examinations and neurocognitive assessments as those in PCI arm. Accordingly, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal & non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurobehavioral functions for our registered patients.

Expected results. This randomized controlled study aims to verify that the incidence of BM still can significantly be reduced by hippocampal-sparing PCI; additionally, NCF preservation regarding neurobehavioral assessments might also be achieved by hippocampal-sparing PCI as compared with the observation arm without PCI. No matter what the final results present, it is believed that this randomized controlled trial (RCT) will provide us solid evidence concerning the exact value of hippocampal-sparing PCI in our patient setting.

Conditions

Non-Small-Cell Lung Cancer (NSCLC); Brain Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PCI via hippocampal-sparing WBRT

All studied patients should undergo a computed tomography (CT) simulation scan encompassing the entire head region with 1.25-mm slice thickness using a thermoplastic mask for immobilization. To achieve conformal hippocampal sparing during the delivery of WBRT, the technique of volumetric modulated arc therapy (VMAT) via Linac-based RapidArc® or TrueBeamTM is employed in our treatment planning. All treatment plans are delivered by using the Linac Varian-iX or TrueBeamTM. In terms of dose prescription, a dose of 30 Gy in 15 fractions is prescribed to whole-brain planning target volume (PTV) under the setting of prophylactic cranial irradiation for NSCLC patients.

Group Type: EXPERIMENTAL

hippocampal-sparing WBRT

Intervention Type: RADIATION

observation without PCI

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

hippocampal-sparing WBRT

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of NSCLC
• Must be adult patients (≥ 18 years old) who have received definitive surgery and have a permanent pathology of nodal metastasis
• Platinum-based chemotherapy is mandatory
• Good performance status better than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky (KPS) > 70 %
• Should have sufficient proficiency in Mandarin language

Exclusion Criteria

• Have received prior cranial irradiation
• Presence of other active primary cancer (exception of basal cell carcinoma of skin and cervical carcinoma in situ)
• Radiographic evidence of brain metastasis/metastases
• Clinical evidence of extracranial metastatic disease
• Hypersensitivity to magnetic resonance (MR) contrast enhancer
• Serious medical or psychiatric illness

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chi-Cheng Yang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Chang Gung University

Shinn-Yn Lin, M.D.

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chi-Cheng Yang, Ph.D.

Role: CONTACT

ccyang@mail.cgu.edu.tw

886-988378478

Facility Contacts

Shinn-Yn Lin, M.D.

Role: primary

rt3126@gmail.com

+886-33281200 ext. 7172

Other Identifiers

103-6591A3

Identifier Type: -

Identifier Source: org_study_id