Clinical trial NCT02887651: Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection
Official title: Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebral Metastases
Surgery
Keywords: cerebrale metastases
radiotherapy
surgery
complete surgical resection
resection
cavity boost radiation therapy
observation
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2016-09-02
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Local tumor control of resected metastases at 6 month
timeFrame: 6 month
Secondary outcomes:
measure: Local tumor control of resected metastases at 12 and 18 month
timeFrame: 12, 18 month
measure: Distant tumor control of resected metastases at 6, 12 and 18 month
timeFrame: 6, 12 and 18 month
measure: Incidence of leptomeningeal carcinosis
timeFrame: 6, 12 and 18 month
measure: Eortc qlq bn20 questionaire
timeFrame: 3, 6, 9 12, 15, 18 month
measure: Eortc qlq c30 questionaire
timeFrame: 3, 6, 9, 12, 15, 18 month
measure: Mini-Mental State Examination (MMSE)
timeFrame: 3, 6, 9 12, 15, 18 month
measure: Hopkins Verbal Learning Test (HVLT)
timeFrame: 3, 6, 9 12, 15, 18 month
measure: Controlled Oral Word Association (COWA)
timeFrame: 3, 6, 9 12, 15, 18 month
measure: Test and Trail-Making Test (TMT) A & B
timeFrame: 3, 6, 9 12, 15, 18 month
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: Heinrich-Heine-University
state: NRW
Study officials:
affiliation: Department of Neurosurgery
name: Michael Sabel, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: department of radiation oncology
name: Wilfried Budach, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: