xRead - Nasal Obstruction (September 2024) Full Articles

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ICAR SINONASAL TUMORS

and late effects of RT. Further large-scale phase III trials are required to define the role of proton therapy in NPC treatment. Role of proton therapy in treatment of NPC

(stage II) cancers would still benefit from the addition of chemotherapy in the era of IMRT. A meta-analysis in 2018 showed no added benefit of concurrent chemotherapy in stage II NPC when treated with IMRT. 1682 A recent phase III RCT showed that for small-volume T2N1 and T3N0 disease, concurrent chemotherapy can be omitted when patients are treated with IMRT. 1683 When comparing the different dosing regimen of cis platin, a meta-analysis showed that there is minimal difference in survival between a weekly regimen and 3 week regimen, but the toxicity profiles are different. 1684 The weekly regimen has less nausea and vomiting and can be administered in a day-chemotherapy clinic setting. However, the 3-week regimen has less marrow suppression and anemia. There was no severe nephrotoxicity (grade 3–4) noted in both regimes and there was no significant difference in the occurrence of mild nephrotoxicity. EGFR monoclonal antibodies such as cetuximab have been used as adjunct treatment for head and neck SCC. The addition of anti-EGFR antibodies with or without concurrent chemotherapy during RT has only been stud ied in small-scale cohort studies or retrospective studies. There are no phase III RCTs studying the effect of anti EGFR when administered during RT. A large retrospective case-controlled study showed no difference in DFS, locore gional failure/recurrence-free survival (LRFS), DMFS, and OS in the anti-EGFR + RT group versus CRT group. 1685 Therefore, EGFR antibodies could be considered as an alternative treatment to cisplatin for patients with poor cisplatin tolerance based on this study. A meta-analysis consisted of four cohorts and one case-controlled study comparing CRT versus CRT + cetuximab showed no dif ference in OS, while there was benefit in DMFS, LRFS, and DFS. However, there were more grade 3 and 4 skin rash, mucositis, and dermatitis in the group treated with additional cetuximab. Another meta-analysis on 12 small cohorts also showed no survival benefits for addi tion of anti-EGFR to CRT. 1686 Therefore, the addition of cetuximab during CRT is not recommended. Role of concurrent chemoradiation therapy in treatment of advanced-stage NPC

Aggregate grade of evidence

C (Level 2: one study)

Benefit

Proton therapy has improved radiation dose falloff, potentially reducing the dosage to normal tissue adjacent to the tumor. Potential risk of marginal miss as the radiation fall off is sharp. Potential “hot spots” resulting in areas of overtreatment. Proton therapy is significantly more expensive than IMRT and is not widely available. Not enough data to conclude. Patient groups that would benefit from proton radiotherapy have not been well defined. Cost may decrease in the future with increased availability of proton treatment facilities. Large-scale phase III trials with economic analysis are required to define the role of proton radiotherapy in the treatment of NPC. Balance of benefits and harms.

Harm

Cost

Benefits–harm assessment

Value

judgments

Policy level Option. Intervention Proton therapy may be considered as primary modality for treatment of NPC at available facilities for the potential benefits of sparing critical SARs. 9 Role of concurrent chemoradiation therapy The landmark Intergroup-0099 trial in 1999 first estab lished the benefit of adding chemotherapy during radio therapy to improve disease control for NPC. 1679 Since then, multiple large RCTs have confirmed the benefit of concur rent CRT. The meta-analysis from the NPC–MAC group summarized the benefit of CRT (Table XXV.6). 1658 CRT improves all survival measures including PFS, LRC, dis tant control, and cancer mortality. The main agent for CRT is cisplatin, usually administered as a 30–40 mg/m 2 weekly or 80–100 mg/m 2 every 3 weeks. Most trials on CRT included advanced-stage III and IV cancers with a few studies also including T2N1 stage II cancers. A large RCT with T1-2N1M0 or T2N0M0 stage II NPC patients, random ized to CRT with weekly cisplatin versus RT alone, showed significant benefit of CRT in OS, PFS, and DMFS at 5 1680 and 10 years. 1681 It is unclear whether patients with T2N0

Aggregate grade of evidence

A (Level 1: one meta-analysis of 4800 patients in 19 trials) The addition of concurrent chemotherapy to radiation in advanced-stage NPC improves OS (HR 0.79), and absolute increase in OS at 5 years is 6.3%.

Benefit

Harm

Increased acute toxicities with CRT.

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