Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection

NCT ID: NCT02887651

Last Updated: 2022-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-14
• Study Completion Date: 2024-12-31

Brief Summary

The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

Detailed Description

The surgical resection of cerebral metastases as a key element in a multimodal therapeutic concept of brain metastatic patients is included in the common recommendations and international guidelines (level I evidence). These recommendations are based on a series of prospective, randomized and controlled studies which addressed the impact of the surgical metastases resection combined with a whole-brain radiation therapy (WBRT) in comparison to WBRT alone. Achieving local tumor control is the major goal of surgery and local tumor control rate after surgery alone has been addressed in few studies: A prospective, randomized American multicenter study revealed a local recurrence rate of 46% by median follow-up of 43 weeks for patients who underwent surgery alone without an adjuvant radiation therapy. Similarly, the 2-year local recurrence rate after metastases resection alone was 53.1% in a retrospective Korean study and 59% in the prospective, randomized and controlled EORTC 22952-26001 study.

In conclusion, standard surgery alone is not sufficient to achieve local control in about 50% of patients (evidence level I). Therefore, surgery of cerebral metastases is often followed by an adjuvant radiation therapy, which is an important part of a multi-modal therapy. Evidence for an additional adjuvant whole-brain radiation therapy (WBRT) after surgical resection was gained from a first prospective, randomized study in 1998: Patients treated by surgery followed by adjuvant WBRT had a significant lower local in-brain progression rate as compared to patients randomized to surgery alone (46% with a median follow-up of 48 weeks in the observation group vs. 10% with a median follow-up of 43 weeks). This result was recently confirmed by the EORTC 22952-26001 study: The 2-year local in-brain progression rate after surgical resection was reduced by a WBRT from 59% to 27%. But despite the lower local and also lower distant in-brain progression rate, the WBRT had no significant influence on the overall survival. The additional analysis of the quality of life data of the EORTC 22952-26001 study showed, that a WBRT negatively impacts the health-related quality of life with a statistically relevant and clinically significant impairment of the physical functioning (at 8 weeks), cognitive functioning and of the global health status. In conclusion, WBRT after surgery of cerebral metastases significantly reduces the incidence of local recurrences but has no impact on the overall survival and has a significant negative impact on the patient´s quality of life and cognitive function. Therefore, WBRT is not mandatory as adjuvant concept after surgical metastases resection and does not have an additional oncological impact in comparison to observation.

A local fractionated radiation therapy in analogy to the WBRT might achieve a similar local tumor control than observation alone but might be associated with an improved cognitive functioning as compared to WBRT. The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

Conditions

Cerebral Metastases; Surgery

Study Design

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

Study Groups

observation

patients in the observation arm receive no adjuvant local radiation therapy after complete surgical resection of a cerebral metastasis

Group Type: NO_INTERVENTION

No interventions assigned to this group

cavity boost radiation therapy

patients in the intervention arm receive an adjuvant local radiation therapy (cavity boost radiation therapy: 10 x 3 Gy ad 30 Gy; clinical target volume (CTV): resection cavity plus surrounding 5 mm; planning target volume (PTV): CTV + 1mm)

Group Type: ACTIVE_COMPARATOR

Cavity boost radiation

Intervention Type: RADIATION

Cavity boost radiation therapy with 10 x 3 Gy for patients suffering from complete resected cerebral metastases

Interventions

Cavity boost radiation

Cavity boost radiation therapy with 10 x 3 Gy for patients suffering from complete resected cerebral metastases

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• histologically confirmed metastasis of carcinoma (except small cell carcinoma) or malignant melanoma
• 1-3 metastases in the preoperative MRI
• Karnofsky Performance Status (KPS) ≥ 70
• Age > / = 18 years
• Recursive partitioning analysis (RPA) 1-2
• life expectation ≥ 6 months
• no previous irradiation of the brain
• MRI examinations possible
• start of the radiation therapy possible within 6 weeks after surgery
• informed consent

Exclusion Criteria

• confirmation of residual tumor in the postoperative MRI
• dementia or disease of central nervous system with a higher risk or radiogenic toxicity
• contraindication for MRIs or lack of acceptance for a MRI
• Glasgow Coma Scale < 12
• Severe concomitant disease: severe cardiac, pulmonary, renal diseases with an increased risk of surgery and radiation
• previous therapeutic irradiation of the brain
• no histological confirmation of carcinoma metastases or malignant melanoma metastases
• cerebral metastases of small cell cancer, undifferentiate neuro-endocrine carcinoma, lymphoma, leucemia, sarcoma or germ cell tumor
• leptomeningeal carcinosis
• distance of the cerebral metastasis to the optic system or radiation sensible brain parts < 10 mm
• metastases of the brain stem, Di- or Mesencephalons, Pons oder Medulla oblongata
• bone marrow dysfunction
• contrast agent allergy
• pregnancy

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

Sponsors

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Sabel, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery

Wilfried Budach, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

department of radiation oncology

Locations

Heinrich-Heine-University

Düsseldorf, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Marcel A. Kamp, MD

Role: CONTACT

marcelalexander.kamp@med.uni-duesseldorf.de

0049 - 211 - 81 - 07461

Facility Contacts

Marcel A. Kamp, MD

Role: primary

marcelalexander.kamp@med.uni-duesseldorf.de

0049-211-81-07461

Other Identifiers

5405

Identifier Type: -

Identifier Source: org_study_id