Definitive and Salvage Radiotherapy Compared to Other Modalities for Laryngeal Carcinoma in Situ

Abstract

We sought to analyze survival endpoints for laryngeal carcinoma in situ (CIS) undergoing definitive radiotherapy (RT) compared to other modalities. Usingour prospectively maintained head and neck cancer database, we identified laryngeal CIS patients treated between 6/2001 and 12/2021. We excluded low-grade dysplasia, CIS with any synchronous invasive squamous cell carcinoma (SCC) within 3 months of the initial CIS biopsy and cases with inadequate follow up. Patients were offered either definitive RT, CO2/KTP laser ablation, photodynamic therapy (PDT) or any sort of therapeutic excision. After first line treatment, follow-up includes visits every 3-6 months with laryngoscopy and biopsies as appropriate. For recurrent CIS beyond 6 months of first line treatment, we reported salvage therapies received and long-term outcomes were reported. Using Kaplan-Meier curves and log-rank test we investigated recurrence free (RFS), progression to invasive SCC free (IFS) and overall (OS) survival across treatment groups. Patients managed with salvage RT were compared to first line RT recipients. Atotal of 85 CIS cases were included: median age 65 years (IQR: 55-74), 73 males (85%) and 70 white (82.4%). 86% had a history of smoking with median pack year of 38 (IQR: 20-55) and 66% had a history of alcohol use. CIS was glottic in most of the cases (90.6%: 66% unilateral, 21% bilateral & 13% involved commissure); with only 9.4% in the supraglottic region. RT was used in 49.4% (n = 42) after biopsy (55%) or surgery (45%) with median dose of 63 Gy/28 fractions, mainly by 3D conformal RT (76%). The remaining 50.6% (n = 43) got therapeutic excision alone (commonly microflap excision) (46.5%), CO2/KTP laser (32.6%) or PDT (20.9%). Demographics and clinicopathological details were non-different between RT and non-RT patients except for Charlson comorbidity index: median 2 (IQR 1-3) in non-RT vs 1 (IQR 0-2) in 1ry RT; p = 0.007. After a median follow-up of 4.8 years (IQR 3.5), 51.8% had recurrent disease, 21.2% progressed to invasive SCC and 9.4% had laryngectomies mainly for invasive SCC after RT. First line RT had improved 2-(83% vs 39%) and 5-(74% vs 22%) year RFS vs non-RT therapies (p<0.001). Nevertheless, 2- and 5-year IFS (89% vs 98% and 80% vs 79%) and OS (92% vs 93% and 81% vs 77%) were non-significant among both (p>0.05 for all). Among non-RT cases with CIS recurrences, 12/35 (34%) had salvage RT. Following RT, salvage RT patients had similar 2- and 5-year RFS (81% vs 83% and 81% vs 74%) and IFS (81% vs 89% and 81% vs 80%) compared to first line RT (p>0.05 for all). All cases with CIS recurrences were salvaged successfully with 100% living with no CIS at latest follow-up. Laryngeal CIS can be treated with a wide range of modalities including 1ry RT which has better recurrence free survival. Nevertheless, non-RT recurrent CIS can be salvaged successfully with many options including RT with equivalent long-term results.