Reirradiation of primary CNS tumors
Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy.
We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas.
Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment.
Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.
Available from: Michael Baumann
- "In contrast to first-line radiotherapy where systematic efforts were undertaken to compare different fractionation regimens, no such randomized comparisons are available. The retrospective series reported by Bauman et al. (1996) included 17 patients with primary CNS tumors, who received hyperfractionated reirradiation and 17 patients treated with once-daily fractionation (Table 1). Some children, e.g., with medulloblastoma were included in this heterogeneous population. "
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ABSTRACT: This chapter summarizes the principles of fractionated radiotherapy and altered fractionation approaches. Clinical reirradiation
examples and isoeffect calculations are provided. The vast majority of published reirradiation series consist of retrospective
data or small prospective studies with limited statistical power. In addition, the typical patient populations are more heterogeneous
than in first-line radiotherapy studies. For example, patients with local relapse, regional relapse, or second primary tumors
might be included. Therefore, the level of evidence is not comparable to that of first-line radiotherapy, where many treatment
recommendations and guidelines are based on large and well-designed prospective randomized trials or meta-analyses of several
trials. Reirradiation is often used for palliative symptoms but occasionally curative approaches, which require high total
radiation doses, might be possible. Hyperfractionated reirradiation might theoretically improve the therapeutic ratio, but
prospective trials are required to confirm this hypothesis.
Available from: Tessy María Lopez Göerne
- "Currently Temozolomide is the best well-tolerated drug that can cross BBB (10–13). In the case of malignant tumors like glioblastoma multiforme (GBM) (13–16), Temozolomide can improve life expectancy by 6 months. Because GBM spreads very rapidly and infiltrates healthy tissue, complete resection is practically impossible, leaving the survival index of patients with GBM rather low even after surgery, radiotherapy, and chemotherapy. "
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ABSTRACT: In vivo suppression of glioblastoma multiforme (GBM) in Wistar rats using silica-shelled biocatalytic Pt(NH(3))(4)Cl(2) nanoparticles is reported. These nanoparticles were synthesized by a sol-gel technique and characterized by SEM and HRTEM imaging. We confirmed morphological uniformity (30 nm) and surface acidity of the nanoparticles, respectively, by TEM imaging and FTIR spectral analysis. Interestingly, treatment of Wistar rats intraperitoneally inoculated with C(6) cells using the biocatalysts resulted in considerable tumor shrinkage. Efficiency of the biocatalyst to shrink a tumor is superior to that by the commercial cytotoxic agent cisplatin. The tumor suppression property of Pt(NH(3))(4)Cl(2) nanoparticles is attributed to catalytic damage of DNA in C(6) cells.
Available from: Daniel Habermehl
- "In the past, a second course of radiotherapy has been applied reluctantly with conventional techniques as treatment outcome outweighs the risk of treatment-related side effects . With modern high-precision stereotactic photon techniques, such as Fractionated Stereotactic Radiotherapy (FSRT) re-irradiation could be established as a safe and effective treatment option for recurrent gliomas . "
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ABSTRACT: Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. METHODS DESIGN: In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival.
The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning.
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