Laser Interstitial Thermal Therapy (LITT) for the Treatment of Pediatric Central Nervous System Tumors

Pediatric brain tumors have a variety of surgical options depending on the location and type
of tumor. Complete or near complete surgical removal of pediatric brain tumors usually
results in the best chance of survival or long-term control of the tumor. Surgical resection
through an open craniotomy is the most common surgical treatment for accessible brain
tumors. For tumors that are not surgically accessible or that are resistant to surgical
intervention, treatment is limited to radiation and or chemotherapy, which can have
significant long term toxicity in children.

Laser interstitial thermal therapy (LITT) offers a minimally invasive surgical option to
treat central nervous system (CNS) tumors. LITT uses laser energy delivered to a target
(i.e. CNS tumor) through a fiberoptic catheter, which results in damage to intracellular
proteins and DNA, and subsequent cell death. LITT provides a sharp demarcation between
ablated and unharmed tissue, which, when combined with the ability to monitor and control
the ablation via MR thermal imaging, results in a high level of precision and control. LITT
may offer a treatment option for patients with deep brain lesions that are surgically
inaccessible, such as tumors located in the thalamus, hypothalamus, basal ganglia and
brainstem. LITT may also be a potential treatment for brain tumors which have recurred or
persist despite conventional therapies including craniotomy. The MRI-guided laser probe used
in LITT utilizes a much smaller surgical corridor through the brain to reach a deep lesion,
potentially reducing the risk of complications.

This study will offer LITT, rather than open craniotomy, for the diagnosis and treatment of
newly diagnosed pediatric brain tumors located in difficult to surgically access regions of
the brain and for the treatment of recurrent/resistant pediatric brain tumors located
anywhere within the brain. The primary aim of this study is to determine if LITT is
effective in reducing (or at least maintaining current rates of) tumor re-growth while
lowering rates of post-surgical complications and improving quality of the procedure (i.e.
shorter hospitalization and less use of pain medication compared to standard surgery for
tumor removal/biopsy).

This study has the following goals:

1. Determine the frequency of post-operative side-effects in pediatric patients with newly
diagnosed, difficult to surgically access CNS tumors or resistant/recurrent CNS tumors
in any location who receive LITT treatment for tumor ablation.

2. Examine the role of LITT in controlling newly diagnosed difficult to surgically access
CNS tumors or resistant/recurrent pediatric CNS tumors in any location.

3. Assess the correlation between the extent of tumor ablation and the rate of local tumor
control.

4. Characterize the MRI changes that occur in a pediatric tumor following LITT ablation.

Patients enrolled on this study will require routine post-LITT follow-up, including
intermittent physical exams to assess for side effects and MRIs to monitor the status of the
tumor. The follow-up is similar to that performed following an open craniotomy and does not
involve any extra studies. The side effects and rate of tumor control for each brain tumor
patient enrolled on the trial will be compared to disease matched historical controls to
learn more about the morbidity and efficacy of LITT in this population of patients compared
to patients who underwent open craniotomy for resection/biopsy.

Inclusion Criteria:

1. Age between 1 and 22 years.

2. Karnofsky Performance Scale (for patients > 12 y/o) or Lansky Performance Score (for
patients < 12y/o) must be > 50 assessed within two-weeks prior to enrollment.

3. Tumor volume less than 10 cm3 is mandatory for high grade tumors.

4. Tumor volume greater than 10 cm3 is acceptable in low grade tumors if the entire
tumor can be ablated in more than one staged procedure.

5. Histology must be available, obtained either at a prior surgery or at the time of
LITT by stereotactic biopsy (except in germ cell tumors where elevation of tumor
markers is diagnostic).

6. Patients must meet the following histological and disease states:

A) Newly diagnosed low-grade CNS tumor located in a site that is difficult to access
surgically or recurrent/persistent low-grade CNS tumor (any site) despite treatment with
conventional therapy. Tumor types include:

1. Grade I or II glioma,

2. Desmoplastic neuroectodermal tumor (DNET),

3. Ganglioglioma,

4. Desmoplastic infantile ganglioglioma/astrocytoma,

5. Choroid plexus papilloma (CPP),

6. Meningioma,

7. Subependymal giant cell astrocytoma (SEGA),

8. Craniopharyngioma

9. Teratoma, or

10. Other "low-grade CNS tumors"

B) Newly diagnosed high-grade CNS tumor located in a site that is difficult to access
surgically or recurrent/persistent high-grade CNS tumors (any site) despite treatment with
conventional therapy. Tumor types include:

1. Grade III or IV glioma,

2. Ependymoma,

3. Atypical teratoid rhabdoid tumor (ATRT),

4. Choroid plexus carcinoma (CPC),

5. Germ cell tumor (GCT),

6. Medulloblastoma/primitive neuroectodermal tumor (PNET),

7. Other "high grade CNS tumors".