Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy of Stereotactic Conformal Radiotherapy (SCRT) Compared to Conventional Radiotherapy in Minimising Late Sequelae in Children and Young Adults With Brain Tumours: a Randomised Clinical Trial
Brief Summary: Brain tumours are the commonest solid tumours in children and the second most common neoplasms overall in this patient population. Radiotherapy plays an important part in the management in a majority of these tumours. While the cure rates of these tumours, especially the benign and low grade ones are quite encouraging, the treatment itself may lead to some late sequelae, which could have significant implications in the quality of life in these long-term survivors.

Stereotactic conformal radiotherapy (SCRT) is a modern high-precision radiotherapy technique, which reduces the volume of normal brain irradiated and has the capability to minimise the doses to critical structures. The present study is designed to prospectively estimate the incidence and severity of neuropsychological, cognitive and neuroendocrine dysfunction following radiotherapy delivered with conventional and stereotactic techniques and would be one of the most comprehensive studies providing very important longitudinal and reliable data regarding these sequelae. The study involving 200 patients would be to the best of our knowledge not only the largest ever study conducted so far but also the only randomised trial assessing these sequelae in patients receiving focal brain irradiation.

The study also examines whether the physical advantages of modern technological progress translate in clinical benefit. This could have significant implications in the radiotherapeutic management of children and young adults with brain tumours. The study is unique in design in terms of evaluating the efficacy of SCRT with respect to conventional radiotherapy in terms of long term tumour control and treatment related complications.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed unifocal or multifocal supratentorial WHO grade II astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic), oligodendroglioma, or oligoastrocytoma
* Patients with neurofibromatosis are eligible
* No other low-grade histologies, including:

  * Pilocytic astrocytoma
  * Subependymal giant cell astrocytoma of tuberous sclerosis
  * Subependymoma
  * Pleomorphic xanthoastrocytoma
  * Presence of a neuronal element such as ganglioglioma
  * Dysneuroembryoplastic epithelial tumor
* No presence of any high-grade glioma, including:

  * Anaplastic astrocytoma
  * Glioblastoma multiforme
  * Anaplastic oligodendroglioma
  * Anaplastic oligoastrocytoma
* No tumors in nonsupratentorial or other locations including optic chiasm, optic nerve(s), pons, medulla, cerebellum, or spinal cord
* No evidence of spread to spinal meninges or noncontiguous cranial meninges (i.e., leptomeningeal gliomatosis)
* No gliomatosis cerebri

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Hematopoietic:

* For high-risk patients:

  * Granulocyte count at least 1,500/mm\^3
  * Platelet count normal

Hepatic:

* Bilirubin no greater than 2 times normal
* SGOT or SGPT no greater than 4 times normal
* Alkaline phosphatase no greater than 2 times normal

Renal:

* Creatinine no greater than 2 times normal

Pulmonary:

* No chronic lung disease (unless DLCO at least 60%)

Neurological:

* Neurologic function score no greater than 3

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
* No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy to the head or neck (unless brain is clearly excluded, such as radiotherapy for localized vocal cord cancer)

Surgery:

* Not specified
B: Inclusion Criteria:

1. Patients with primary intracranial tumours such as low-grade glioma, meningioma, craniopharyngiomas, ependymomas and other benign tumours considered for radical focal radiotherapy.
2. Tumours measuring upto 7 cms on maximum dimension on the CT/MRI.
3. Age 3 to 25 years.
4. NPS of 0-3.
5. Informed consent from patients or parents as appropriate.
6. Long-term follow up expected

Exclusion Criteria:

1. Previous radiotherapy.
2. Planned adjuvant chemotherapy.
3. Expected median survival of less than two years.
4. Patient not cooperative for planning and execution of SCRT.
C: Inclusion criteria: Diagnosis: newly diagnosed glioblastoma in elderly patients

1. Signed informed consent
2. Age \> 65 years
3. Newly diagnosed supratentorial glioblastoma
4. Eligible for first infusion of bevacizumab \> 28 and \> 49 days after surgery for glioblastoma
5. Karnofsky performance score 60 or more
6. Paraffin-embedded tissue for central pathology review
7. Stable or decreasing corticosteroid dose within 5 days prior to enrolment
8. Adequate haematological function:
9. Adequate liver function
10. Adequate renal function

Exclusion criteria:

1. Karnofsky performance score 50 or less
2. Evidence of recent hemorrhage on postoperative brain MRI
3. Tumor with infiltration of retina, optic nerve, optic chiasm or brainstem
4. Any prior chemotherapy including carmustine-containing wafers (Gliadel®) or immunotherapy for glioblastoma or lower grade astrocytomas
5. Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field
6. Inadequately controlled hypertension
7. History of hypertensive crisis or hypertensive encephalopathy
8. New York Heart Association (NYHA) grade II or higher congestive heart failure
9. Myocardial infarction or unstable angina within 6 months prior to enrolment
10. Stroke or transitory ischemic attack within 6 months prior to enrolment
11. Other significant vascular disease within 6 months prior to enrolment
12. History of = grade 2 haemoptysis within 1 month prior to enrolment
13. Bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
14. Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury within 28 days prior to first dose of bevacizumab
15. Core biopsy (excluding intracranial biopsy) or other minor surgical procedure within 7 days prior to first dose of bevacizumab
16. Abdominal fistula or gastrointestinal perforation within 6 months prior to enrolment
17. Intracranial abscess within 6 months prior to enrolment
18. Serious non-healing wound, active ulcer or untreated bone fracture
19. Pregnancy or lactation
20. Fertile women \< 2 years after last menstruation and men unwilling or unable to use effective means of contraception
21. Active malignancy that may interfere with the study treatment at the investigator?s and PI discretion
D: Inclusion Criteria:

* Patients must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received CAN-2409 + prodrug on this study may receive an additional CAN-2409 + prodrug course at recurrence if eligibility criteria are still met.
* Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
* Upfront patients must be planning to undergo standard radiation therapy.
* Patients must be 18 years of age or older.
* Performance status must be KPS ≥70.
* Patients must have SGOT (AST) \< 3x upper limit of normal.
* Patients must have serum creatinine \< 2mg/dl and calculated creatinine clearance \>10ml/min.
* Patients must have platelets \> 100,000/mm3 and WBC \> 3000/mm3.
* Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
* Patients must give study specific informed consent prior to enrollment. For re-administration, patients must be re-consented.
* Patients must be able to tolerate MRI scan procedure

Exclusion Criteria:

* Active liver disease including cirrhosis or hepatitis
* Patients on immunosuppressive drugs (with exception of corticosteroid)
* Known HIV+ patients.
* Patients with acute infections (viral, bacterial or fungal infections requiring therapy).
* Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
* Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
* Other serious co-morbid illness or compromised organ function.
* Patients may not receive chemotherapy until valacyclovir is completed and may not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from CAN-2409 injection until tumor progression).

Answer: B