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AIM: Data from a local quality registry are used to model the risk of late xerostomia after radiotherapy for head and neck cancer (HNC), based on dosimetric- and clinical variables. Strengths and weaknesses of using quality registry data are explored. METHODS: HNC patients treated with radiotherapy at the Karolinska University hospital are entered into a quality registry at routine follow up, recording morbidity according to a modified RTOG/LENT-SOMA scale. Other recorded parameters are performance status, age, gender, tumor location, tumor stage, smoking status, chemotherapy and radiotherapy data, including prescribed dose and organ-at-risk (OAR) dose. Most patients are entered at several time points, but at variable times after treatment. Xerostomia was modeled based on follow-up data from January 2014 to October 2018, resulting in 753 patients. Two endpoints were considered: maximum grade ≥2 (XERG≥2) or grade ≥3 (XERG≥3) late xerostomia. Univariate Cox regression was used to select variables for two multivariate models for each endpoint, one based on the mean dose to the total parotid volume (Dtot) and one based on the mean dose to the contralateral parotid (Dcontra). Cox regression allows the estimation of the risk of xerostomia at different time points; models were presented visually as nomograms estimating the risk at 9, 12, and 24 months respectively. RESULTS: The toxicity rates were 366/753 (49%) for XERG≥2 and 40/753 (5.3%) for XERG≥3. The multivariate models included several variables for XERG≥2, and dose, concomitant chemotherapy and age were included for XERG≥3. Induction chemotherapy and an increased number of fractions per week were associated with a lower risk of XERG≥2. However, since the causality of these relationships have limited support from previous studies, alternative models without these variables were also presented. The models based on the mean dose to the total parotid volume and the contralateral parotid alone were very similar. CONCLUSION: Late xerostomia after radiotherapy can be modeled with reasonable predictive power based on registry data; models are presented for different endpoints highly relevant in clinical practice. However, the risk of modeling indirect relationships, given the unavoidably heterogeneous registry data, needs to be carefully considered in the interpretation of the results.
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BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.
