Efficacy of 5-aminolevulinic acid based photodynamic therapy in pituitary adenomas-experimental study on rat and human cell cultures.

BACKGROUND: Incomplete resection of pituitary adenomas may result in recurrence. As adjuvant irradiation is not riskless, alternative treatment options should be investigated. 5-aminolevulinic acid based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. The present study examined the efficacy of 5-ALA PDT in vitro on benign pituitary adenoma cell cultures. METHODS: In group I experiments were performed on immortalized rat pituitary adenoma cells (GH3). The cultured cells were treated with different 5-ALA concentrations ranging from 7.5-16.5µg/ml. In Group II human pituitary adenoma cell cultures were obtained from surgically resected adenoma tissue (n=15). These were incubated with 5-ALA concentrations from 12.5-100µg/ml. The concentration ranges had been determined in preliminary dose-finding tests. For both groups incubation time was four hours and PDT was performed by exposition to laser light (635nm, 625s, 18.75J/cm(2)). Cell viability was examined by WST-1 assay. RESULTS: In both groups PDT showed a 5-ALA concentration-dependent effect on cell death. In group I lower 5-ALA concentrations were necessary to destroy all cells as compared to group II. Moreover, in group II, the different subtypes of human adenomas showed different sensitivities to 5-ALA-based PDT (secreting vs. non-secreting). Especially corticotroph adenomas were highly sensitive to 5-ALA PDT. CONCLUSIONS: The GH3 cell line was an useful in vitro model to optimize different PDT parameters. Human pituitary adenoma cells could also be killed by 5-ALA PDT, however this required higher 5-ALA concentrations. Furthermore, the results suggested different 5-ALA sensitivities between different human adenoma cell types. More experiments are necessary to confirm these preliminary results.

Feasibility of the EORTC/NCIC Trial Protocol in a Neurosurgical Outpatient Unit: The Case for Neurosurgical Neuro-Oncology.

OBJECTIVE: With the publication of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (EORTC/NCIC) trial, concomitant radiochemotherapy followed by intermittent chemotherapy became the new treatment standard for patients with primary glioblastoma. Eight years after widespread introduction of this protocol, it is of interest to investigate whether this new standard has been established in daily neuro-oncologic practice. We were particularly interested in its practicality within a neurosurgical neuro-oncologic setting. PATIENTS AND METHODS: We analyzed primary glioblastoma patients diagnosed between 2005 and 2013 treated at our center according to the EORTC/NCIC trial. Parameters associated with treatment performance (interruption of radiotherapy, concomitant chemotherapy and intermittent chemotherapy, total number of cycles, and side effects) were retrospectively analyzed and compared with the available data from the EORTC/NCIC trial. RESULTS: In this single-center retrospective study, we identified 189 patients (116 men, 73 women; median age: 62 years) who were treated according to the EORTC/NCIC trial protocol. A total of 176 patients received cytoreductive surgery; 13 patients had stereotactic biopsy only (EORTC/NCIC trial: 239 patients and 48 patients, respectively). Radiotherapy had to be interrupted in 9 patients (5%) (EORTC/NCIC trial: 15 patients [5%]) and concomitant chemotherapy in 26 patients (14%) (EORTC/NCIC trial: 37 patients [13%]). In 156 patients (83%), adjuvant TMZ chemotherapy was initiated (6 median temozolomide [TMZ] cycles; range: 1-30). In the EORTC/NCIC trial, 223 patients (47%) received the intermittent chemotherapy protocol (median: 3 cycles; range: 1-7). Overall, 97 patients (62%) completed 6 TMZ cycles (EORTC/NCIC-trial: 105 patients [47%]); dose escalation to 200 mg/qm at the second cycle was performed in 91 patients (58%) (versus 149 patients [67%]). Intermittent TMZ therapy was discontinued in 59 patients (38%) (versus 118 patients [53%]). Median overall survival in our patient cohort was 19 months (versus 14.6 months); median time to progression was 9 months (versus 6.9 months). CONCLUSION: Comparison between the feasibility of the treatment protocol established by the EORTC/NCIC trial (performed within the setting of a prospective randomized trial) and the daily routine in a dedicated neurosurgical neuro-oncologic department demonstrates that the protocol is suitable for daily practice within a neurosurgical unit.