xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.23262, Wiley Online Library on [02/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

122

KUANetal.

loss, and soft tissue necrosis/fibrosis. 442 While these studies reflect promising treatment outcomes related to PBT’s physical dosimetry, further proton research focus ing on technical improvements, including dynamic arc and biologic enhancement (e.g., RBE optimization, FLASH, proton boron capture therapy), may further impact the therapeutic ratio. 467 In summary, retrospective cohort studies and a sys tematic review show that PBT allows for target coverage maintenance, high-dose RT conformity, and low- and moderate-dose radiation bath reductions (Table XIV.2). The magnitude of LRC, DFS, and OS rate benefits depends on the extent of disease and pathology of the primary malignancy. While IMRT is the standard therapy for SNM at most cancer centers, PT (particularly PBT) may pro vide further benefits in LRC and DFS rates and should be considered when available. C Fast neutron radiotherapy While initial studies (particularly for head and neck and salivary gland malignancies) showed higher disease con trol rates compared to photon therapies, only a few centers worldwide have adopted and maintained the capacity to use NRT. While this initial promise in both retrospec tive and randomized trials showed improved LC rates, progress was stifled by concerns about higher toxicity rates. In addition, improvements in conventional photon conformity and the shielding requirements of neutrons (among others) lead to NRT’s near abandonment. This is despite improvements in beam profile safety that may make neutron delivery more practical for treatment. 468,469 Douglas et al. studied 279 patients, of which 43 had SNM. The 6-year LRC and DSS rates were 59% and 67%, respec tively, and grade 3 or higher complications were seen in 10% of patients. More recently, neutrons have been used in combination with PBT. In 2021, Aljabab et al. pub lished a combined NRT–PBT cohort of 29 patients with unresectable skull base salivary gland tumors, including 12 SNM patients. LC, PFS, and OS rates were 90%, 79%, and 93%, respectively. Ten late grade 3 or 4 events were documented. 463 In summary, retrospective cohort studies show that NRT can improve LRC, PFS, and OS rates in SNM, with the mag nitude of the benefits dependent on the extent of disease and pathology of the primary malignancy (Table XIV.3). However, almost all data were collected on patients treated before 2000 without three-dimensional isodose dose dis tribution evaluation and plan review. Therefore, any comparison of NRT within the literature is not equiva lent to modern outcomes with IMRT, PBT, or CIRT, as it was conducted without modern, surrounding medical

Filtenborg et al. reviewed a 331-patient nationwide clinical database (DAHANCA), showing that guideline compli ance and a combined treatment approach reduced the incidence of LRF and thereby increased OS. 465 In summary, retrospective cohort studies corroborate multiple single-institute studies demonstrating that IMRT allows for the maintenance of target coverage and avoid ance of critical organs at risk (OARs) for SNM. The magnitude of locoregional control (LRC), DFS, and OS rate benefits depend on the extent of disease and pathology of the primary malignancy. IMRT is the standard therapy for photon radiation delivery for SNM at advanced cancer centers. B Proton beam therapy PBT is the most widely available particle therapy for treating superficial and deep-seated tumors. Like IMRT, PBT allows for high-dose conformity, which is critical for the sensitive OARs adjacent to the skull base. In addi tion, PBT may also allow low- and moderate-dose reduc tions. Despite these benefits, the present treatment cost and geographic availability are limiting factors for PBT’s widespread utilization. Favorably, a single cost–benefit analysis showed that PBT for SNM provided an extra 1.65 quality-adjusted life-year (QALY) at an additional cost of $38,929 compared with IMRT, with an incremental cost effectiveness ratio of $23,611/QALY. 466 This was secondary to improved DFS compared to IMRT, as demonstrated in a 2014 systematic review and meta-analysis. Patel et al. demonstrated that pooled OS and DFS rates were signif icantly higher at 5 years for PBT than for photon therapy (relative risk [RR] 1.51, 95% CI: 1.14–1.99; p = 0.0038 and RR 1.93, 95% CI: 1.36–2.75; p = 0.0003, respectively). Subgroup analysis specifically identified that PBT provided improved LRC (RR 1.26; p = 0.011) 5 years after treatment and DMFS rates (RR 1.44; p = 0.045) at the longest follow-up. 458 In one of the largest published PBT series, Dagan et al. reviewed 143 patients at the University of Florida; the 5 year LRC rate was 78%, and the OS rate was 59%. Surgery improved LC rates, but only with GTR (5-year LC for GTR 87% vs. subtotal resection [STR] 62.9% vs. biopsy alone 55%; p = 0.001), and gross residual disease was the only sig nificant prognostic factor for LRC rates on multivariate analysis. Late grade 3 toxicities were high at 22% (32 of 143), including central nervous system necrosis in 6% (9 of 143) and vision loss in 3.5% (five of 143). 460 Fan et al. evaluated 86 prospective patients with PBT. The 2-year LC and OS rates for radiation-naive patients were 83% and 81%, respectively. Nearly 25% experienced acute grade 3 toxicities, and 6% experienced late grade 3 toxicities, including osteoradionecrosis (ORN), vision