3466 - Timing of Pre- vs. Post-Radiation Weekly Cisplatin Infusion for SCC of the Head and Neck or Cervix Uteri and Impact on Outcomes
Presenter(s)
C. M. B. Fitch1, A. Niemierko2,3, R. D. Merkin2,4, T. J. Roberts2,4, A. L. Russo5, D. N. Margalit6, and J. J. Paly2,7; 1Harvard Radiation Oncology Program, Mass General Brigham, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Department of Radiation Oncology, Mass General Brigham/ Massachusetts General Hospital, Boston, MA, 4Department of Medicine, Harvard Medical School, Boston, MA, 5Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 6Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 7Department of Radiation Oncology, Harvard Medical School, Boston, MA
Purpose/Objective(s): Weekly cisplatin dosed to 40 mg/m2 delivered concurrently with radiation therapy (RT) is now an accepted dosing regimen in management of squamous cell carcinoma (SCC) of the head and neck (HN) or cervix uteri. Pharmacodynamic studies have suggested rapid cisplatin clearance following infusion, which may theoretically impact synergy with concurrent RT, but the clinical implications of infusion timing before vs after daily RT remain a matter of debate. This retrospective cohort study examined whether weekly cisplatin infusion before vs after RT impacts locoregional disease control.
Materials/Methods: Patients with newly diagnosed SCC of the HN or cervix between January 2014 and June 2025 managed non-surgically with definitive RT (= 60 Gy) and concurrent weekly cisplatin at 40 mg/m2 in a large academic hospital system were identified from an institutional database. Univariable and multivariable Cox regressions analyzed associations between cancer-related outcomes (overall survival [OS], locoregional control [LRC]) and sequencing of cisplatin infusion with RT on infusion day. Cisplatin sequencing (CS) was analyzed both categorically (=50% or =66% of cycles infused before RT on infusion day) and continuously (number of cycles infused prior to RT). LRC was the primary endpoint, and OS was a secondary endpoint, both calculated from the biopsy date. An exploratory analysis was performed in the subset of HN patients without p16+ oropharynx (OPX) SCC given the more aggressive nature of this disease.
Results: 441 patients with SCC of the HN (n = 396) or cervix (n = 45) were eligible for analysis. 66% of all HN patients had p16+ OPX SCC. 82% of HN patients were male. The median age was 61 years. Median follow-up was 4.0 years (IQR 1.9 - 6.1). The median number of cisplatin cycles received was 6 (IQR 5-7). 68.5% of patients received cisplatin prior to RT on =50% of infusion days. CS was not associated with LRC or OS on univariate or multivariable Cox regression for the entire cohort (=50% cycles pre-RT: HR 0.96, P = 0.86 for MVA of PFS) or when evaluated as a continuous variable. MVA found worse LRC in AJCC 8th ed. Stage III/IV (HR1.71, P = 0.05), induction chemo (HR 2.08, P = 0.01), active smoking (HR 1.88, P = 0.05). Exploratory analysis of HN patients without p16+ OPX disease (n = 137) indicated a non-significant trend toward improved LRC with CS before RT (HR 0.50, p = 0.13 for =66% before RT).
Conclusion: In a mixed cohort of patients with advanced HN and cervix SCC receiving concurrent chemoRT with weekly cisplatin 40mg/m2, there was no LRC or OS benefit observed when delivering cisplatin prior to RT on infusion days. A trend toward improved LRC in the subset of patients with p16 negative HN disease warrants further investigation in a larger sample size.