Photodynamic therapy in the treatment of brain tumours. A feasibility study.

BACKGROUND: Photodynamic therapy (PDT) constitutes a treatment modality that combines a photosensitizing agent with exposure to laser light in order to elicit phototoxic reactions that selectively destroy tumor cells and spare normal cells. PDT is a local treatment modality without long-term systemic effects. Its application can be repeated more than once to the same area without accumulative effects. METHODS: Patients diagnosed with primary brain tumors were treated with PDT. Treatment consisted in administration of the photosensitizer followed by craniotomy, surgical resection and laser illumination of the surgical bed. Primary brain tumors received also temozolomide-based chemotherapy and radiotherapy (RT). RESULTS: From May 2000 to December 2010, 41 patients (27 male, 14 female) with a median age of 49 years (range 13-70) diagnosed of primary brain tumors were included in the study. In 7 patients PDT was repeated at the time of the relapse. In 22 episodes PDT was part of the initial treatment of primary brain tumors and in 26 episodes was part of the treatment at relapse. Median PFS observed was 10 months for GBM (95% confidence interval 5.7-14.3), 26 months for AA (95% CI 4.5-47.5), and 43 months for OD (95% CI 4.5-47.5). Median OS was 9 months for GBM (95% CI 2.3-15.7), 20 months for AA (95% CI 0.0-59) and 50 months for OD (95% CI 32.5-67.5). The apparent discrepancy between PFS and OS data is due to patients not censored for PFS because they die from causes other than tumor progression. Median OS since first diagnosis was 17 months for GBM (95% CI 15.2-17.8), 66 months for AA (95% CI 2.9-129.1) and 122 months for OD (95% CI 116.1-127.8). Side effects were mild and manageable. CONCLUSIONS: This study confirms that PDT can be considered as an adjunctive to surgery and/or RT and chemotherapy in the treatment of brain tumors, excluding those patients with thalamic or brain stem locations. It adds therapeutic effect without adding significant toxicity. In order to improve its contribution, it is essential to find new drugs with more penetration in order to destroy tumor cells more deeply at resection margins.

Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer.

Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.