What are the contraindications for Radiation Therapy (RT) in patients with Central Nervous System (CNS) tumors?

Contraindications of Radiation Therapy in CNS Tumors

There are no absolute contraindications to radiation therapy for CNS tumors; however, RT should be avoided or deferred in specific clinical scenarios where risks outweigh benefits, including poor performance status (KPS <70 without glioblastoma), very young age (<3 years when possible), pregnancy, and certain genetic conditions like neurofibromatosis where RT may induce secondary malignancies.

Relative Contraindications Based on Performance Status

Poor performance status represents the most clinically relevant contraindication to standard radiation therapy:

• Patients with KPS <70 and glioblastoma should receive hypofractionated RT, chemotherapy alone, or palliative care rather than standard fractionated RT 1
• For patients with anaplastic gliomas and KPS <70, hypofractionation is preferred over standard fractionation if RT is pursued, though chemotherapy or palliative care remain alternatives 1
• The complexity of symptoms and handicaps from malignant gliomas makes performance status an imperfect measure of fitness, requiring individualized assessment beyond simple KPS scoring 1

Age-Related Considerations

Age represents a critical factor in determining RT appropriateness, particularly at extremes:

• Radiation should be avoided or deferred until after age 3 years in pediatric CNS tumors when feasible to minimize neurodevelopmental toxicity 2
• For elderly patients (>70 years) with glioblastoma and poor performance status, the NCCN panel specifically recommends against chemoradiation due to lack of supporting data 1
• Elderly patients with good performance status may receive hypofractionated RT as a category 1 recommendation, which is better tolerated than standard fractionation 1

Genetic and Syndromic Contraindications

Neurofibromatosis requires special consideration but is not an absolute contraindication:

• Patients with neurofibromatosis can receive RT for CNS tumors with local control rates similar to non-NF patients, though careful risk-benefit assessment is essential 3
• The theoretical concern about radiation-induced secondary malignancies in NF patients must be weighed against tumor progression risk 3

Pregnancy

Pregnancy represents a strong relative contraindication to cranial RT:

• While not explicitly detailed in the provided guidelines, standard radiation oncology practice defers RT during pregnancy when possible due to potential fetal risks, even with cranial treatment
• Surgical management or observation should be prioritized when feasible until after delivery

Prior Radiation Exposure

Previous whole-brain radiation therapy creates significant constraints for re-irradiation:

• Patients who previously received WBRT should not undergo repeat WBRT due to neurotoxicity concerns 1, 4
• Re-irradiation is only a category 2B option if prior RT produced a good/durable response (>6 months) 1
• Accumulated doses must remain below approximately 100-120 Gy2 EQD2 to brain parenchyma to avoid unacceptable toxicity 4
• Focal techniques like stereotactic radiosurgery should be considered instead of repeat WBRT 4

Disease-Specific Considerations

Certain tumor types and clinical scenarios warrant RT deferral:

• Low-grade gliomas (WHO grade 2) in young patients with complete resection and favorable prognostic factors may defer RT until progression 1
• Pilocytic astrocytomas are curable with surgery alone and do not require RT 1
• For oligodendroglioma WHO grade 2 with positive prognostic factors (complete resection, younger age), initial therapy may be deferred 1

Systemic Disease Considerations for Metastases

For brain metastases, systemic disease status influences RT appropriateness:

• Patients with systemic disease progression and limited systemic treatment options should receive palliative care or consider reirradiation only if prior RT was effective 1
• Untreated or active brain involvement is a contraindication to high-dose interleukin-2 therapy for melanoma, though RT can address this before systemic therapy 1

Technical and Anatomic Contraindications

Certain technical factors may preclude specific RT modalities:

• Metal implants create artifacts that interfere with target delineation and affect dose calculation, particularly for particle therapy 4
• Life-threatening mass effect, hemorrhage, or hydrocephalus requires palliative neurosurgery before RT can be considered 1

Common Pitfalls to Avoid

• Do not automatically exclude elderly patients from RT based solely on age—performance status and tumor biology are more important determinants 1
• Do not defer RT indefinitely in high-risk low-grade gliomas (>2 EORTC risk factors), as these patients benefit from early upfront RT 1
• Do not assume all patients with poor performance status cannot receive RT—hypofractionated regimens (20 Gy in 5 fractions) may be appropriate for palliation 1
• Do not overlook the need for multidisciplinary review involving neurosurgeons, radiation oncologists, medical oncologists, and neurologists before finalizing treatment decisions 1