Photodynamic Applications in Brain Tumors

Abstract

Malignant brain tumors (MBTs) encompass primary malignant brain tumors (PMBTs) and secondary brain tumors (SBTs). MBTs affect 5-10 out of 100,000 people annually and are responsible for 3% of all cancer deaths worldwide. These tumors are the second most common cause of cancer death in young people and the sixth most common cause of productive-years-loss in the community. MBTs carry very dismal prognosis and their diagnosis almost always means a death sentence deferred by merely 36 weeks or less (Obwegeser et al. 1995; Eljamel 2004). PMBT (intracranial gliomas) represent 38%–40% of primary brain tumors and glioblastoma multiforme (GBM) is the most common PMBT (Stupp 2007). GBMs are divided into two: primary and secondary GBMs. Primary GBMs arise de novo, represent 60% of GBMs, and are diagnosed mainly in people over 50 years of age. Secondary GBMs, on the other hand, represent 40% of GBMs and are most common in people under 45 years of age. Several researchers have studied GBMs extensively to assess their prognosis and factors associated with better survival. Three risk groups were identified (Lamborn, Chang, and Prados 2004): a low-risk group consisting of young patients (under 40 years of age) with tumors located in the frontal lobe; a moderaterisk group consisting of patients between 40 and 65 years of age and Karnofsky performance scores (KPSs) >70 who had surgical resection; and a high-risk group of patients >65 years of age and patients between 40 and 65 years who had KPS <80 or had tumor biopsy only. Several recent studies assessed the impact of genetic mutations on GBMs’ outcome (Rich et al. 2005; Kleihues, Burger, and Cavenee 1997). Loss of heterozygosity (LOH) on chromosome group 10q, the most frequent gene abnormality for both primaryand secondary GBMs, is associated with poor survival. It occurs in 60%–90% of GBMs. This mutation appears to be specific for GBMs and is found rarely in other tumor grades. Mutations of p53, a tumor suppressor gene, were among the first genetic alterations identified in astrocytic brain tumors and appear to be deleted or altered in approximately 25%–40% of all GBMs and particularly in secondary GBMs (Watanabe et al. 1997). Despite extensive clinical trials, the median survival remained about 12 months with fewer than 25% surviving for 2 years and fewer than 10% surviving for 5 years. In a series of 279 patients, only five (1.8%) survived for 3 years (Scott et al. 1998). Clearly, newer approaches for the management of GBMs are necessary and multimodality therapeutic approaches would be required to improve the outcome of these tumors. The joint tumor section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) in 2008 produced guidelines for the management of newly diagnosed GBMs (Olsen et al. 2008). The authors recommended maximum safe surgical resection of newly diagnosed GBMs (evidence level II), followed by 60 Gy of postoperative radiotherapy to the enhancing lesion (evidence level I) and for radiotherapy to include a 2 cm cuff around the enhancing lesion (evidence level II). The guidelines also recommended concurrent and postoperative temozolomide in newly diagnosed GBM (evidence level I) and BCNU (carmustine wafers) in those who undergo craniotomy (evidence level II). Temozolomide offers a mere 26% 2 year survival compared to 10% in placebo controls, a 14.6 month median survival compared to 12.1 months in placebo group, and a 7.2 month tumorprogression-free (TPF) survival compared to 5 months among placebo controls (Olsrn et al. 2008). Carmustine implants, on the other hand, prolong survival to 13.9 months compared to 11.942.1 Introduction ............................................................................................................................ 485 42.2 PD in MBT ............................................................................................................................... 486Fluorescence Image-Guided Surgery • Fluorescence Image-Guided Biopsy 42.3 PDT in MBT ............................................................................................................................ 48942.4 Specific Brain PD and PDT Equipment .............................................................................. 493 42.5 Conclusions.............................................................................................................................. 493 References ............................................................................................................................................ 493months in the placebo group (Vecht et al. 1990). The poor outcome of these tumors is due to local invasion and local relapse. The vast majority of these tumors recur locally within 2 cm of the resection margin and patients often succumb to and die from local recurrence, indicating that a more aggressive local therapy is required to eradicate these tumors. However, complete radical surgical excision is hindered by the elusive nature of these tumors: a significant amount of tumor cells are invisible to the naked eye even with the aid of the surgical microscope. The ability of these cancers to disguise themselves makes their identification at surgery almost impossible. Most of these tumors have invaded the brain widely by the time they manifest clinically, making wider excision margin out of the question in most cases par polar lesions in noneloquent brain.