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KUANetal.

TABLE XXV.3 (Continued)

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusion

Huang et al. 1656 No association between oncogenic HPV and carcinogenesis or prognosis of WHO II and III NPCs in Taiwanese patients Abbreviations: LRC, local–regional control; NCDB, National Cancer DataBase; OS, overall survival; PFS, progression-free survival; SEER, Surveillance, Epidemiology, and End Results. 2011 4 Retrospective case–control 43NPC (15HPV + , 28HPV– Prevalence of HPV

Role of nasopharyngectomy for NPC

5 Primary radiation therapy of the primary site NPC is one of the first cancers successfully treated with pri mary RT (Table XXV.5). 1669 Conventional two-dimensional radiotherapy (2DRT) techniques had been used for treat ment of NPC since the 1960s until the advent of 3DRT and IMRT. There are many critical structures at risk (SARs) adjacent to tumors of the skull base, especially in locally advanced cases. With 2DRT technique, the radiation toler ance of these structures limits the dose of radiation that can be delivered to the primary tumor without signifi cant toxicity. With 3DRT and IMRT, high-dose RT can be contoured to the tumor, ensuring better delivery of ade quate radiation dosage without surpassing the dose limit for SARs. Multiple phase II trials have shown the effi cacy of IMRT in local control and reducing toxicities. A large phase III RCT showed better LRC with IMRT com pared to 2DRT in T4 and N2 disease, improved OS in N2 and stage III disease, and marginally improved OS in stage IVA disease. Two-dimensional RT is associated with more acute and late toxicities. 1670 Two meta-analyses, one including phase II/III RCTs and one including addi tional nonrandomized cohorts, showed that IMRT has superior OS and PFS with reduced late toxicities compared to 2DRT techniques. 1671,1672 Therefore, IMRT is strongly recommended in treatment of all stages of NPC both for superior disease control and less toxicity. Role of IMRT in treatment of NPC

Aggregate grade of evidence

C (Level 2: two studies; Level 4: 17 studies)

Benefit

ENPG has become an effective treatment for patients with early local recurrent NPC, demonstrating good survival outcomes and low complication rates. It avoids not only the severe side effects caused by re-irradiation but also complications (e.g., functional problems and cosmetic morbidities) that may be encountered during traditional open approaches. Positive margins, especially around critical neurovascular structures; risk of ICA injury leading to intraoperative and postoperative hemorrhage; wound infection; injury to surrounding critical neurovascular structures. ENPG may have a lower cost than re-irradiation because of the relatively shorter treatment duration and ensuring faster recovery. Current data suggest that ENPG is a promising treatment option for most patients with early-stage local recurrent NPC, with minimal complications. However, only one RCT has been conducted. Although selected patients with advanced-stage recurrent NPC may benefit from ENPG, long-term follow-up is needed to evaluate the eventual morbidity from and efficacy of the procedure. Balance of benefits and harms.

Harm

Cost

Benefits–harm assessment

Value

judgments

Policy level Option. Intervention ENPG is a good option for early local

Aggregate grade of evidence

A (Level 1: two studies; Level 2: three studies)

recurrent NPC (rT1 and rT2 and select rT3 lesions), with limited complications and promising outcomes. Meticulous preoperative evaluation and a full understanding of the surgical anatomy are

Benefit

IMRT improves OS and LRC in locally advanced NPC and reduces long-term toxicities including xerostomia, trismus, and temporal lobe neuropathy in all stages. IMRT has no additional harm compared to conventional 2DRT.

Harm

important to prevent significant complications such as ICA injury.

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