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

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CHERAGHLOU ET AL .

that includes approximately 70% of all newly diagnosed malignancies in the United States from over 1500 cancer pro- grams, as previously described. 30 This study was determined to be exempt from institutional review by the Yale Human Investigation Committee. 2.2 | Study population Our selection criteria are presented in Figure 1. We identified cases with a primary site in the parotid, submandibular, or sublingual glands by the International Classification of Dis- ease for Oncology, third edition topography codes C07.9 5 parotid gland (n 5 7162), C08.0 5 submandibular gland (n 5 1063), C08.1 5 sublingual gland (n 5 94), C08.8 5 over- lapping lesion of major salivary glands (n 5 10), C08.9 5 major salivary gland, and not otherwise specified (NOS; n 5 251). We included the following histology codes: 8430 (mucoepidermoid); 8550 (acinar); 8200 (adenoid cystic); 8140 (adenocarcinoma, NOS); and 8940 and 8941 (malig- nant mixed), with all other subtypes being included as other/ unknown. We excluded patients if they were under 18 years old at the time of diagnosis, did not receive surgery as part of their definitive treatment, had any other malignancies, had distant metastases, had gross residual disease after surgery, received combined therapy outside the therapeutic time win- dows, as described in the following section, did not receive a therapeutic dose of radiation ( < 44 Gy), had missing follow- up, had missing pathologic T classification, had missing pathologic N classification, or had insufficient data for risk stratification. Data were insufficient for risk stratification where adverse features, as noted in Figure 1, were not pres- ent but data on 1 or more features were missing. A minimum dose of 44 Gy was selected as this is the lowest recom- mended dose for therapeutic adjuvant radiation according to the NCCN guidelines. 5 2.3 | Statistical analysis Staging was based on the American Joint Committee on Cancer (AJCC) criteria in the year of diagnosis. Patients were considered having early-stage disease if they had an AJCC pathologic stage of 1 or 2 and late-stage disease if they had an AJCC pathologic stage of 3 or 4. Early-stage and late-stage groups were then further subdivided based on the presence or absence of any adverse feature. These adverse features were selected based on the NCCN treatment guidelines, which identified them as indications for adjuvant therapy and included: adenoid cystic histology, intermediate/ high-grade, positive surgical margins, or pathologic node involvement. Surgical margins were classified as negative and positive. We defined no residual tumor as negative margins; and resid- ual tumor, NOS, and microscopic residual tumor as positive

malignancies with and without adverse features, such as nodal involvement or close/positive margins. 6 – 16 With this improved control, patients treated with adjuvant radiotherapy are less likely to develop recurrent disease. This potential benefit must be weighed against the sequelae of radiation to the head and neck, which includes a number of symptoms that can affect quality of life, such as: mucositis, loss of taste, xerostomia, osteoradionecrosis, radiation caries, and trismus. 17 – 19 It may also be inferred that better control may lead to improved sur- vival, in which case radiation sequelae become more accepta- ble. A number of single-institution studies have demonstrated this trend. 7,9,12,20 – 22 Additionally, Mahmood et al 23 reported improved survival for patients with high-grade and/or locally advanced (T3/T4 or N 1 ) disease who were treated with sur- gery and adjuvant radiotherapy opposed to surgery alone in a larger analysis of the Surveillance, Epidemiology, and End Results registry. However, the application of conclusions from this work to modern clinical practice is difficult. Most did not restrict analysis to patients with the adverse features currently recommended to undergo adjuvant radiotherapy, 7,9,12,22 whereas others did not differentiate between early-stage dis- ease with adverse features and late-stage disease with or with- out adverse features. 20,21,23 There has yet to be a large-scale study exploring the stage-specific survival benefits received from adjuvant radiotherapy for salivary gland cancers. Evidence for the use of adjuvant chemoradiotherapy for these malignancies is also sparse. Apart from small, single- institution studies, 24,25 there is a lack of evidence in the liter- ature for the use of adjuvant chemotherapy in salivary gland tumors beyond its use for inoperable or metastatic disease. Recent studies have suggested increased toxicity and no sur- vival benefit associated with the addition of chemotherapy to the standard adjuvant therapy of postoperative radiotherapy of salivary gland malignancies. 26 – 29 A Radiation Therapy Oncology Group clinical trial aiming to address the efficacy of adjuvant chemoradiotherapy is ongoing and has an esti- mated completion date of October 2023 (NCT01220583). The purpose of this study was to explore the relationship between adjuvant therapy after surgery for salivary gland malignancies and patient survival. We had a secondary objective of determining whether there was a survival benefit associated with the addition of chemotherapy to the adjuvant therapy of these cancers. To accomplish this, we examined a cohort of 8580 patients from the Commission on Cancer ’ s National Cancer Data Base (NCDB) who were diagnosed between 2004 and 2013 inclusive. 2 | MATERIALS AND METHODS 2.1 | Data source Data originated from the NCDB from 2004 to 2016. The NCDB is a nationwide clinical surveillance resource dataset

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