What are the current guidelines for nasopharyngeal cancer radiotherapy?

Current Guidelines for Nasopharyngeal Cancer Radiotherapy

Intensity-modulated radiotherapy (IMRT) with daily image guidance is the mandatory standard technique for all patients with nasopharyngeal carcinoma, delivering 70 Gy in 33-35 fractions to gross disease and 50-60 Gy to at-risk regions. 1

Radiotherapy Technique

IMRT is non-negotiable and represents the only acceptable modern radiotherapy approach for NPC. If IMRT is unavailable at your institution, patients must be transferred to facilities capable of delivering IMRT. 1 This strong recommendation is based on meta-analyses demonstrating significant improvements in 5-year overall survival and local control compared to conventional 2D or 3D techniques, along with substantial reductions in late xerostomia, trismus, and temporal lobe injury. 1

• Daily image guidance must be implemented to minimize setup variation during high-precision radiotherapy and enable monitoring of anatomic changes during treatment. 1

• Both sequential boost and simultaneous integrated boost (SIB) techniques are acceptable, with SIB preferred as the technique of choice due to convenience and resource efficiency while maintaining equivalent efficacy and toxicity profiles. 1 A phase III RCT of 209 patients confirmed no difference in clinical outcomes between these approaches. 1

Dose Prescription

The standard prescription is 70 Gy in 33-35 fractions (2.0-2.12 Gy per fraction) delivered over 7 weeks (once daily, 5 fractions per week) for macroscopic disease. 1 This fractionation was validated in the Intergroup 0099 and RTOG 0225 trials, demonstrating good efficacy with acceptable toxicity. 1

• Elective treatment of at-risk sites requires 50-60 Gy. 1

• Dose adjustments may be considered based on tumor response: For patients with MRI-detected residual tumor at completion of IMRT, an additional 2-4 Gy boost in 1-2 fractions may be given. For very responsive small primaries, a slightly lower total dose (66-68 Gy) may be considered. 1

• Never use fraction sizes >2.12 Gy per fraction, especially with concurrent chemotherapy, due to unproven efficacy and substantial risk of late toxicity to adjacent neurological structures. 1, 2

Target Volume Delineation

MRI fusion with CT simulation is absolutely mandatory for all NPC target delineation - this is not optional. 1, 2 MRI is essential to appreciate tumor extension at the skull base, rule out or confirm cranial nerve involvement, and identify intracranial extension. 1

Gross Tumor Volume (GTV)

• GTV must be carefully delineated following international consensus guidelines with exploitation of MRI-CT fusion capabilities. 1, 2

• For patients receiving induction chemotherapy, the preinduction scan must be fused with post-induction CT simulation to illustrate initial disease extent. 1, 2

• GTV should generally follow the preinduction tumor extent, especially within bony anatomy at the skull base. 1, 2 Do not reduce GTV at skull base after induction chemotherapy unless intermediate dose (≥64 Gy) covers the pre-induction extent. 2

Elective Nodal Volumes

Bilateral neck coverage from retropharyngeal lymph nodes to levels II-V is standard due to high incidence of occult nodal involvement. 1

• Level Ib may be omitted unless there is involvement of the anterior half of the nasal cavity, or level II lymph nodes with extranodal extension or size >2 cm, or bilateral involvement. 1

• Omission of lower neck volume in the uninvolved side may be considered if the neck contains no equivocal lymph nodes. 1 A randomized trial showed upper versus whole-neck prophylactic RT led to similar lower neck control rates in node-negative NPC. 1

Stage-Specific Treatment Algorithms

Stage I Disease

• IMRT alone is the standard treatment. 1

Stage II-IVA Disease

• Stage T1-2N1 and all Stage III-IVA disease require concurrent chemoradiotherapy with cisplatin. 1

• Induction chemotherapy followed by concurrent chemoradiotherapy may be offered for Stage II (T0-T2N2) and Stage III-IVA disease. 1

• Adjuvant chemotherapy alone has not been documented to confer survival advantage and its role remains debatable. 1 A randomized trial of adjuvant cisplatin and gemcitabine versus observation in patients with persistent EBV DNA showed no improvement in relapse-free or overall survival. 1

Critical Pitfalls to Avoid

• Never contour without MRI-CT fusion - CT alone misses critical disease extent at skull base and perineural involvement. 1, 2

• Do not use accelerated fractionation with multiple fractions >1.6 Gy/fraction to minimize risk of late neurological toxicity. 1

• Avoid excessive dose to temporal lobes as T stage, addition of chemotherapy, and maximal RT dose to temporal lobe are significant risk factors for temporal lobe necrosis. 1

• Do not omit elective nodal irradiation in N0-stage disease - bilateral neck coverage is commonly practiced due to high risk of occult involvement. 1

Emerging Technologies

Proton therapy represents a promising approach for locally advanced NPC to maintain high RT dose while avoiding neurological structures. 1 Small studies with relatively short follow-up have shown significantly lower rates of severe mucositis and salivary dysfunction when IMRT is followed by proton therapy boost compared to full-course IMRT alone, though this remains investigational. 1