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Metastasierte Tumore

CYBER-SPACE Studie

Cyberknife radiosurgery for patients with brain metastases diagnosed either SPACE or MPRAGE sequence - A prospective randomized evaluation of response and toxicity.

Summary

For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Newer findings have shown that for patients with more than four lesions SRS can be considered as a favorable alternative to whole-brain radiotherapy (WBRT), the currently established standard-of-care treatment. With modern techniques highly conformal SRS of multiple lesions has become feasible with comparable clinical effort and minimal toxicity as compared to WBRT. Developments in magnetic resonance imaging (MRI- imaging) have produced highly sensitive contrast-enhanced three-dimensional fast spin echo sequences such as SPACE that facilitate the detection of very small and early-stage lesions in a fashion superior to the established Magnetization Prepared Rapid Gradient Echo (MPRAGE) series.

Since it has been established that the response of brain metastases to SRS is better for smaller lesions and that WBRT can come at the price of significant neurotoxicity, the investigators hypothesize that 1) earlier detection of small brain metastases and 2) early and aggressive treatment of those by SRS will result in an overall clinical benefit by delaying the failure of repeated localized therapy and thus preserving quality of life and potentially prolonging overall survival. On the other hand however, overtreatment might be a valid concern with this approach since it has yet to be proved that a clinical benefit can be achieved.

The current study aims to stretch the boundaries of the term "cerebral oligometastases" by performing SRS for up to ten cerebral metastases, compared to the established clinical standard of four, given that existing data supports the non-inferiority of this approach and given that modern Cyberknife SRS facilitates the treatment of multiple lesions with minimal treatment-associated toxicity.

Inclusion criteria

  • radiologically confirmed metastases of the brain with an underlying history of a malignant illness
  • between one and ten suspect intracranial lesions, taking into consideration all available series of the pre-therapeutic MRI (performed at Heidelberg University Hospital and including SPACE sequence)
  • age ≥ 18 years of age
  • Karnofsky Performance Score (KPS) ≥ 70
  • for women with childbearing potential, (and men) adequate contraception.
  • ability to understand character and individual consequences of the clinical trial
  • written informed consent (must be available before enrolment in the trial)

Exclusion criteria

  • refusal of the patient to take part in the study
  • Small-cell lung cancer (SCLC) as primary malignant illness
  • More than 10 suspect intracranial lesions in the initial pre-therapeutic MRI imaging (performed at Heidelberg University Hospital and including SPACE sequence)
  • metastasis so close to OAR that initial single-session SRS would be impossible due to lacking radiotolerance
  • known contraindications against the performing of cranial MRI
  • previous radiotherapy of the brain
  • Patients who have not yet recovered from acute toxicities of prior therapies
  • Pregnant or lactating women
  • Participation in another clinical study or observation period of competing trials, respectively

ENCEPHALON Studie

Whole brain radiation therapy (WBRT) alone versus radiosurgery (SRS) for patients with 1-10 brain metastases from small cell lung cancer.

Zusammenfassung

Patients suffering from small cell lung cancer (SCLC) are at high risk for developing brain metastases (BM). To prevent a clinical manifestation of preexisting microscopic brain dissemination, prophylactic cranial irradiation (PCI) is offered to both limited and extensive disease patients, if they respond to first line regime, thus being at risk or at chance to develop clinical brain metastases. However, up to 10-15% of patients present with BM at initial diagnosis. If MRI is used as a diagnostic tool for initial staging the number even increases up to 15-20%. Additionally, between 40 - 50% of patients develop BM until time of death and the risk of developing BM further increases with prolonged survival. Treatment options are usually limited to WBRT and palliative chemotherapy but the actual effect of therapeutic WBRT has mainly been studied in small retrospective and nonrandomized studies. WBRT has been established as the treatment standard in patients with cerebral metastases from SCLC, however, it has only modest efficacy. Results might be improved by additional dose escalation. A SRS to cerebral metastases may be indicated in patients with intracranial disease, and the current protocol is aimed at exploring the neurocognition and efficacy of SCLC in patients with brain metastases treated with SRS or WBRT.

The present trial aims to exploratory investigate the treatment response to ´conventional whole brain radiotherapy´ (WBRT) and ´stereotactic radiotherapy´(SRS) in SCLC patients.

Einschlusskriterien

  • histologically confirmed small cell lung cancer
  • MR-imaging confirmed cerebral metastasis (not resected, maximum number of 10)
  • age ≥ 18 years of age
  • For women with childbearing potential, (and men) adequate contraception.
  • Ability of subject to understand character and individual consequences of the clinical trial
  • Written informed consent (must be available before enrolment in the trial)

Ausschlusskriterien

  • refusal of the patients to take part in the study
  • previous radiotherapy of the brain
  • Patients who have not yet recovered from acute high-grade toxicities of prior therapies
  • Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
  • Pregnant or lactating women
  • Participation in another competing clinical study or observation period of competing trials, respectively
  • MRI contraindication (i.e. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants)
  • KPS <60
  • Simultaneous cytotoxic chemotherapy
  • Last application of chemotherapy/immunotherapy/targeted therapy <1 week before cerebral radiotherapy

ESTRON Studie

Evaluation of Stereotactic Radiotherapy of the Resection Cavity after Surgery of Brain metastases compared to post-operative whole-brain radiotherapy.

Zusammenfassung

In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are becoming increasingly important as well as good loco-regional disease control of brain metastases.

Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative.

Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1).

This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS).

Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).

Einschlusskriterien

  • histologically confirmed solid cancer
  • MRI confirmed cerebral metastases
  • Neurosurgical resection of one cerebral metastasis
  • age ≥ 18 years of age
  • Karnofsky Performance Score ≥ 60
  • for women with childbearing potential, (and men) adequate contraception.
  • ability to understand character and individual consequences of the clinical trial written informed consent (must be available before enrolment in the trial)

Ausschlusskriterien

  • refusal of the patients to take part in the study
  • previous radiotherapy to the brain
  • 10 unresected brain metastases in postoperative MRI
  • Patients who have not yet recovered from acute toxicities of prior therapies
  • known carcinoma < 2 years ago (excluding carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
  • pregnant or lactating women