xRead - Nasal Obstruction (September 2024) Full Articles

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KUANetal.

Morbidity following radiation treatment including osteoradionecrosis

neutropenia, leukopenia, thrombocytopenia, anemia, alopecia, stomatitis, infections, nausea, vomiting, anorexia, diarrhea, and hearing loss, consistent with the literature. 2164–2166 For platin/etoposide regimens, the most frequent severe AEs reported are secondary to myelosuppression, with severe neutropenia seen in many patients. 2167,2168 Multiple trials have examined cyclophosphamide/doxorubicin/vincristine, and the most common severe AEs are myelosuppression, infection, alopecia, and neuropathy. 1832,2169,2170 A meta-analysis by Kim et al. comparing patients receiving IC with TPF plus CRT versus those receiving CRT alone found higher rates of myelosuppression in the IC cohort, with no difference in the rates of nonhematologic toxicities. 2171 These authors also found a higher risk of not completing CRT in the IC cohort, a finding that is replicated in other studies. 2172 CRT is frequently used in SNM, with a variety of regimens used depending on tumor histology. Overall, cis platin is best studied and most widely applied. Typical adverse effects of CRT are due to both the AEs from the chemotherapeutic agents themselves as well as in-field RT effects, and include hematologic side effects, mucositis, stomatitis, and dermatitis. 2173,2174 Ye et al. retrospectively analyzed a multi-institutional cohort of 349 patients with head and neck cancer of all subsites treated with CRT with cisplatin or cetuximab and found grade 3/4 toxicities in 58% and 45% in each group, respectively, most commonly oral mucositis and radiation dermatitis, as well as a 34% and 20% rate of unplanned hospital admissions, respectively, consistent with other similar studies. 2175,2176 InanRCTby Bonner et al. comparing CRT with cetuximab versus RT alone, the authors found no exacerbation of RT-related AEs, including xerostomia, pain, and mucositis, with the addition of cetuximab. 2177 Intra-arterial chemotherapy for SNM is performed with the goal of maximizing chemotherapy dose to the tumor while minimizing systemic toxicity. An RCT by Rasch et al. compared intra-arterial to IV cisplatin concurrent with chemoradiation for stage IV head and neck cancer of multiple subsites. They found lower rates of grade 3 or more renal toxicity and a higher rate of grade 3 or more neurologic toxicity in the intra-arterial group ver sus the IV group, but no other significant difference in toxicities. 2178 Long-term follow-up from this trial after a median of 7.5 years showed higher rates of dysphagia and esophageal toxicity in the intravenous group, but no difference in xerostomia, mucositis, or nephrotoxicity. 2179 A cohort study by Homma et al. examining specifically SNM patients similarly found moderate rates of toxic ity with intra-arterial chemotherapy concurrent with RT, with the most common acute toxicities including mucosi tis and nausea/vomiting, and most common late toxicities including osteonecrosis, brain necrosis, and ocular/visual

Aggregate level of evidence

C (Level 2: one study; Level 3: 12 studies; Level 4: six studies) RT is associated with improved disease control for most pathologies and stages of SNM. Proton beam may reduce RT morbidity, but data are mixed. SNM RT is associated with both early and late toxicities, including mucositis, dermatitis, nasal morbidity, xerostomia, and dysphagia. Severe side effects, such as blindness and brain necrosis, are proportional to the volume and dose of RT, and the morbidity of RT is intensified in the re-irradiation setting. Skull base ORN is rare and management is primarily surgical. Cost comparison analyses have not been undertaken. Preponderance of benefits over harms. Treatment of SNM with RT is frequently indicated for improved disease control; however, it does cause both short- and long-term morbidities. Proton beam RT may be considered to reduce side effects. For ORN, medical management may be attempted but management is typically surgical. RT is associated with improved local control and survival for many tumors but leads to impaired QOL, principally affecting sinonasal symptoms. Acute symptoms are common, as are long-term toxicities. Proton therapy can be considered for a reduction in morbidity. Skull base ORN can be managed medically or surgically, with growing evidence suggesting safety and efficacy. Recommendation.

Benefit

Harm

Cost

Benefits–harm assessment

Value

judgments

Policy level Intervention

F Morbidity following chemotherapy For SNM, chemotherapy is usually given as either induction or concurrently with radiation in the defini tive or adjuvant setting. Depending on pathology, IC is typically with docetaxel/cisplatin/5-fluorouracil (5FU) (TPF), cisplatin or carboplatin/etoposide, or cyclophos phamide/doxorubicin/vincristine. Most chemotherapy trials include patients from all head and neck subsites, not just SNM. In a trial comparing TPF to cisplatin/5FU alone in the induction setting for unresectable head and neck cancer, the most frequent severe AEs were