2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

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CHERAGHLOU ET AL .

associated with this treatment. This is especially salient as 43% of patients with early-stage disease with adverse fea- tures and 27.9% of patients with late-stage disease with adverse features in our sample did not receive any adjuvant therapy. This represents a significant number of individuals who may have improved survival with more widespread treatment in accordance with the national guidelines. Although the discrepancy between guidelines and treat- ment practices in this case may be due to the rarity of sali- vary cancers 1 and a corresponding lack of clinical experience with them for many practitioners, we also identified a num- ber of factors that influence the likelihood of treatment with adjuvant therapy for patients with late-stage disease with adverse features in particular. Within this group, black patients were less likely to receive adjuvant therapy. Under- treatment among black patients has been reported for a num- ber of other conditions 34 – 43 and is a key contributor to racial disparities in disease outcomes. 44,45 Additionally, academic facilities were less likely to use adjuvant therapy for this group. Given the higher rate of guideline adherence among academic facilities noted in studies of other cancers, 46 it is not clear why adjuvant therapy is not as readily utilized in academic facilities for patients with late-stage disease with adverse features. Although radiotherapy to the head and neck has unfavorable treatment sequelae, 17 – 19 increased usage in accordance with the NCCN guidelines among academic facilities as well as work to eliminate racial disparities in treatment may lead to significant improvements in survival among patients with salivary cancers. Notably, we did not find that patients with early-stage or late-stage adenoid cystic histology benefited from improved survival from adjuvant therapy without consideration of the presence of other adverse features. Previous work has shown that although adjuvant radiotherapy does not seem to improve survival for adenoid cystic tumors, it improves locoregional control. 47 Given the proclivity of this histologic subtype for aggressive behaviors, such as perineural invasion leading to high local recurrence rates, 48 – 52 improved control may be a valuable target even in the absence of a survival benefit. Addition of adjuvant chemotherapy was not associated with a survival benefit over adjuvant radiotherapy alone for patients with late-stage disease with adverse features in this analysis. These results, when combined with recently pub- lished work, 26,29 suggest that the survival benefit associated with the addition of chemotherapy to postoperative radiother- apy may be limited. Given the increased toxicity associated with added chemotherapy, 27 further study should be targeted to identify whether added chemotherapy provides enough survival benefit to justify the sequelae of treatment. Random- ized trials, such as Radiation Therapy Oncology Group 1008 (NCT01220583), should shed further light on the utility of chemotherapy in the adjuvant treatment of salivary gland

received surgery with adjuvant chemoradiotherapy. A num- ber of factors were associated with the likelihood of added chemotherapy to adjuvant therapy (Figure 6). Male sex (HR 1.239; P 5 .029); increased nodal involvement; adenocarci- noma (OR 1.943; P < .001) or malignant mixed histology (OR 1.829; P 5 .005); high tumor grade (OR 2.162; P 5 .004); and positive surgical margins (OR 1.833; P < .001) were associated with an increased likelihood of added chem- otherapy. Both patient age over 70 years (OR 0.405; P < .001) and treatment at a nonacademic facility (OR 0.718; P < .001) were associated with a lower likelihood of added chemotherapy. In the present analysis, we found that administration of adju- vant therapy after surgery for salivary gland malignancies was associated with improved survival for patients with any adverse features. Specifically, adjuvant treatment improved outcomes for patients with early-stage disease with either intermediate-/high-grade tumor, adenoid cystic tumor histol- ogy, or positive surgical margins, as well as for patients with late-stage disease with any of the previously mentioned fea- tures or nodal metastases. These data support the NCCN guidelines that suggest that these patients should receive adjuvant therapy because there is a survival advantage FIGURE 6 Factors associated with the addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse fea- tures. Note: The error bars represent 95% confidence intervals (CIs). The figure size was restricted for clarity, the right-side of the error bar for N classification of 3 extends to 25.410 (odds ratio 9.080; 95% CI 3.244- 25.410) 4 | DISCUSSION

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