MO192: Renal Outcomes in High Dose Cisplatin in Locally Advanced Squamous Cell Cancer of the Head and Neck: A Monocentric Experience
Authors: Trevisani Francesco , Floris Matteo , Quattrini Giulia , DI Marco Federico , Lepori Nicola , Cinque Alessandra , Mirabile Aurora 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Head and neck cancer (HNC) represents the sixth most common neoplasm worldwide, accounting for 400 000 deaths globally every year. Among HNC, the squamous cell carcinoma (SCCHN) is the most aggressive histology, being responsible for more than 90% of cases. The overall 5-year survival rate goes from 33% to 68% according to risk factors and primary site.
In clinical practice, at least two cycles of three-weekly high-dose cisplatin (100 mg/m2) concomitant to radiotherapy represents the standard of care given LA-SCCHN with a curative intent, both in postoperative and conservative settings.
However, concurrent high-dose cisplatin is associated with significant acute and late toxicities. Acute kidney injury (AKI) is a common and serious side effect of high-dose cisplatin-based concurrent chemoradiation (CRT). AKI is a predictor of immediate and long-term adverse outcomes. The aim of this study was to investigate the nephrotoxicity of chemotherapy in real life of LA-SCCHN patients during and after treatment with high-dose cisplatin-based CRT, with a particular focus on AKI onset.

METHOD
Ninety-three consecutive patients affected by LA-SCCHN and treated with high-dose cisplatin-based CRT were enrolled in a prospective observational monocentric study. All patients received adequate supportive care such as SF 750 mL + 16 mEq MgSO4 IV 200 mL/h before and after cisplatin administration (a total of 1500 mL at day 0 and again at day 1), with 375 mL mannitol 10% if diuresis after hydration was less than 100–200 mL/h and dexamethasone 12 mg IV as chemo premedication at day 0 and 8 mg PO at days 1 to 3 as antiemetic prophylaxis followed by 6 days of steroid progressive decalage. Demographic data, medical history, and clinical, laboratory and histological data at presentation were reported from the medical records. Serum creatinine was recorded at baseline and after each cycle of treatmentat day 1 and day 10, respectively. eGFR was calculated using CKD-EPI 2012 formula. Bayesian linear regression was used to evaluate the impact of the clinical and pathological features on eGFR decay through cycles and AKI incidence.

RESULTS
The cohort was composed of 93 patients with a median age of 59 years, M/F ratio 2.4, median BMI 24.9 (IQR: 22.3, 27.4), median eGFR 92.2 mL/min. A total of 58% of patients presented basal eGFR &gt; 90 mL/min, while 42% &lt;90 mL/min (only 4 patients with eGFR &lt; 60 mL/min). Approximately 34.4% patients presented hypertension, and the 8.6% were diabetics.
AKI onset was 22.6% in the overall cohort: among those 21 patients who developed AKI, no one showed stage II-III AKI according to the KDIGO classification. Using a definition of AKI based only on an increase in serum creatinine &gt; 1.5 higher than 1.5 times the baseline value, AKI incidence was 14% with a significative difference (P = .04) between patients with baseline eGFR &gt; 90 mL/min and patients with eGFR &lt; 90. Statistical analysis preformed using a logistic regression model showed a correlation between arterial hypertension and AKI incidence, while other comorbidities (such as diabetes) and concurrent medications were not associated with an increased in AKI incidence.

CONCLUSION
AKI was a common complication of high-dose cisplatin treatment in our LA-SCCHN patients’ cohort (22.6%): interestingly, the totality of AKI cases was represented by stage I AKI. The main risk factor for AKI development was a diagnosis of arterial hypertensions (Figure 1), while no correlation with concomitant medications and diabetes was found. The overall AKI incidence in our cohort was lower than reported in previous Studies, likely due to the use of a preventive protocol based on hydration and mannitol use; among those patients who developed AKI, no modification in cisplatin treatment scheme were needed, particularly all the patients reached a cumulative cisplatin dose ≥200 mg/m2.