Acute and Late Toxicities in Patients with Collagen Vascular Disease Receiving Curative-Intent Intensity-Modulated Radiotherapy to the Head and Neck Region

Abstract

Historically, collagen vascular disease (CVD) was considered at least a relative contraindication to radiotherapy (RT). However, more recent meta-analyses suggest that for patients with certain CVDs such as rheumatoid arthritis (RA), there may not be an increased risk for severe toxicities, while for patients with CVDs such as systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma, there may be as high as a 2- to 4-fold risk for severe toxicities compared to patients without CVD. There are also data to suggest that patients with head and neck cancer (HNC) and comorbid CVD are at especially high risk of severe toxicities from RT. This study evaluated the hypothesis that among patients with HNC treated with curative-intent intensity-modulated radiation therapy (IMRT), patients with SLE or DM were more likely to have had late grade ≥3 toxicity rates compared to patients with other CVDs. A total of 23 patients who had HNC with comorbid CVD and received IMRT between 2005-2022 were included. Acute (≤90 days after completion of RT) and late (>90 days) toxicities were retrospectively classified using CTCAE v5.0. Toxicity rates were compared across CVD groups using Chi-squared tests. Median follow-up was 56.3 months. The most common CVDs were RA (9 patients, 39%), SLE (4 patients, 17%), and DM (4 patients, 17%). Median total RT dose was 66 Gy (range: 48-70 Gy), in 1.8-2.4 Gy fractions. Nine (39%) patients received concurrent chemotherapy. 14 (61%) patients had mucosal squamous cell carcinoma (SCC), 3 (13%) had cutaneous SCC, 2 (9%) had nasal cavity/paranasal sinus tumors, 2 (9%) had salivary gland tumors, 1 (4%) had cutaneous melanoma, and 1 (4%) had mucosal melanoma. Eight (35%) patients experienced acute grade ≥3 toxicities, and 3 (13%) patients experienced late grade ≥3 toxicities (Table 1). No patients had grade≥4 toxicities. Patients with SLE or DM did not have significantly higher risk of late grade ≥3 toxicities compared to those with other CVDs (25% vs. 7%, p = 0.21). In this small sample size of patients with HNC and comorbid CVD, definitive or post-operative IMRT was associated with approximately 35% acute and 15% late severe toxicity rates. While SLE/DM were associated with >3-fold late grade ≥3 toxicities, this association needs to be confirmed with larger data sets.