What are the guidelines for re-irradiation (repeated radiation therapy) in head and neck cancer?

Re-irradiation in Head and Neck Cancer

For localized recurrent head and neck cancer, re-irradiation should be strongly considered in selected cases, particularly when delivered postoperatively after salvage surgery, as this approach achieves 5-year overall survival of approximately 49% compared to only 13-20% with definitive re-irradiation alone. 1, 2, 3

Patient Selection and Feasibility Assessment

Re-irradiation is feasible when high-dose radiation can be delivered without exceeding organ-at-risk (OAR) dose constraints, requiring accurate reconstruction of the previous radiation dose distribution and careful assessment of expected cumulative toxicity. 1

Key decision points for proceeding with re-irradiation:

• Surgical resectability status is the primary determinant - postoperative re-irradiation after salvage surgery yields superior outcomes (5-year locoregional control 46% vs 20% for definitive re-irradiation) 2, 3
• Time interval from initial radiation - intervals >3 years between treatments are associated with improved overall survival 2
• Ability to deliver adequate dose while respecting OAR constraints - if adequate target coverage cannot be achieved without exceeding dose limits, alternative treatment modalities are preferable 1

Critical Dose Constraints for Re-irradiation

The carotid artery cumulative dose constraint of 120 Gy is the most critical safety threshold, as exceeding this significantly increases risk of carotid blowout syndrome, a life-threatening complication. 1, 4

Specific cumulative dose constraints supported by outcomes data:

• Carotid arteries: maximum cumulative dose 119-120 Gy (sensitivity 1.00/specificity 0.89 for preventing blowout) 4
• Bone structures: near-maximum cumulative dose 119 Gy to minimize osteoradionecrosis risk 4
• Spinal cord, brain, and aorta: preliminary tolerance data available but dose constraints not firmly established 1

Treatment Approach and Technique

Intensity-modulated radiation therapy (IMRT) is the preferred technique for re-irradiation, showing borderline improved locoregional control (49% vs 36%) without increased late complication rates compared to conventional techniques. 3

Dose and Fractionation

• Postoperative re-irradiation: 60-66 Gy (2.0 Gy/fraction) to high-risk areas including microscopically positive margins and extracapsular nodal extension 5
• Definitive re-irradiation: median cumulative doses of approximately 119 Gy have been reported, though optimal dosing remains undefined 2
• Concurrent chemotherapy consideration: while cisplatin 100 mg/m² every 3 weeks is standard for initial treatment 5, 6, concurrent chemoradiation with re-irradiation shows poor 5-year survival (13%) and significantly increased toxicity risk 2, 3

Advanced Radiation Modalities

High linear energy transfer (LET) radiation such as carbon ions should be considered for re-irradiation after initial low-LET treatment, as it may be more effective against radio-resistant clones selected by the first treatment. 1

Expected Outcomes

Oncologic Outcomes

• 5-year overall survival: 34% overall, 49% for postoperative re-irradiation, 20% for definitive re-irradiation 2
• 5-year locoregional control: 46% for postoperative re-irradiation vs 20% for definitive re-irradiation 3
• Event-free survival (survival without recurrence and without grade ≥3 toxicity): 31% at 5 years 2

Prognostic Factors

Favorable prognostic indicators:

• Postoperative re-irradiation (vs definitive) 2, 3
• Treatment with radiation alone (vs concurrent chemoradiation) 2
• Interval >3 years between initial radiation and re-irradiation 2
• Absence of lymphovascular invasion 7
• Complete response to treatment 7

Toxicity Profile and Management

Serious late toxicity (grade ≥3) occurs in approximately 43-45% of patients at 5 years, representing the major limitation of re-irradiation. 2, 3

Specific Toxicities

• Carotid blowout syndrome: life-threatening complication requiring particular caution when re-irradiating the carotid artery 1, 4
• Osteoradionecrosis: associated with cumulative bone doses >119 Gy 4
• Treatment-related mortality: approximately 5% (3 of 58 patients in one series) 2

Functional Outcomes

Re-irradiation significantly increases dependency on supportive interventions:

• Tracheotomy dependency increases by 20% (p=0.011) 7
• PEG-tube dependency increases by 23% (p=0.003) 7

These functional impacts must be discussed with patients during informed consent, as they substantially affect quality of life.

Palliative Re-irradiation

Low-dose re-irradiation with palliative intent is appropriate only in selected cases where it can be performed with negligible risk of toxicity. 1

For most patients with unresectable recurrence who cannot tolerate curative-intent re-irradiation, palliative chemotherapy remains the standard option, with cetuximab plus platinum-based chemotherapy (cisplatin or carboplatin plus 5-fluorouracil) as first-line treatment for fit patients. 1

Critical Caveats

• Metal implants (e.g., spine stabilization hardware) create CT/MRI artifacts that interfere with target delineation and dose calculation, potentially contraindicating particle therapy 1
• Timing is critical: keep total time from surgery to completion of postoperative re-irradiation as short as possible, ideally <6 weeks 5, 6
• Approximately 1 in 3 patients survive re-irradiation without recurrence and severe complications, highlighting the delicate balance between effectiveness and toxicity 2