Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology A competing risk nomogram to predict severe late toxicity after modern re- irradiation for squamous carcinoma of the head and neck ☆ Matthew C. Ward a,b, ⁎ , Nancy Y. Lee c , Jimmy J. Caudell d , Alexander Zajichek e , Musaddiq J. Awan f , Shlomo A. Koyfman g , Neal E. Dunlap h , Sara J. Zakem i , Comron Hassanzadeh j , Samuel Marcrom k , Drexell H. Boggs k , Derek Isrow l , John A. Vargo m , Dwight E. Heron m , Farzan Siddiqui l , James A. Bonner k , Jonathan J. Beitler n , Min Yao f , Andy M. Trotti d , Nadeem Riaz c , on behalf of the Multi-Institution Re-Irradiation (MIRI) Collaborative a Levine Cancer Institute, Atrium Health, Charlotte, NC, United States b Southeast Radiation Oncology Group, Charlotte, NC, United States c Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States d Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States e Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States f Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, United States g Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland OH, United States h Department of Radiation Oncology, University of Louisville, Louisville, KY, United States i Department of Radiation Oncology, University of Colorado, Denver, CO, United States j Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States k Department of Radiation Oncology, University of Alabama, Birmingham, AL, United States l Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, United States m Department of Radiation Oncology and Division of Head and Neck Surgery, Department of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States n Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, United States ARTICLE INFO Keywords: Reirradiation Recurrent Second primary Salvage Head and neck Toxicity ABSTRACT Purpose: Severe late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. However, many patients experience complications from tumor progression before manifesting late effects. We constructed a nomogram to examine this relationship between late toxicity and competing risks. Methods and materials: Patients with RSP squamous carcinoma originating in a field previously irradiated to ≥40 Gy and treated with IMRT-based re-irradiation to ≥40 Gy were collected. Grade ≥3 late toxicity devel- oping ≥90 days after re-irradiation was collected. A multivariable competing-risk model was fit to the actuarial risk of late toxicity with progression or death as the competing risk. The final bootstrap optimized model was converted into a nomogram. Results: From 9 institutions, 505 patients were included. The 2-year incidence of grade ≥3 late toxicity was 16.7% (95% CI 13.2–20.2%) whereas progression or death was 64.2% (95% CI 59.7–68.8%). The median freedom from late toxicity, progression or death was 10.7, 5.5 and 3.2 months for RPA class I-III patients re- spectively, whereas the median OS was 44.9, 15.9 and 7.9 months, respectively. The final model included six clinical factors. Notably, dose, volume and fractionation did not significantly impact toxicity. Conclusions: After re-irradiation, the risk of progression or death is approximately four times the risk of radia- tion-related severe late toxicity. The risk of late toxicity may be more dependent on patient and disease factors than modifiable treatment factors. This model is useful for patient selection, pre-treatment consent and post- treatment survivorship following re-irradiation. https://doi.org/10.1016/j.oraloncology.2019.01.022 Received 21 November 2018; Received in revised form 11 January 2019; Accepted 26 January 2019 ☆ Presented as digital ePoster at the 59th ASTRO Annual Meeting, September 24–27, 2017, San Diego, California. No grant funding was necessary for the preparation of this data and manuscript. ⁎ Corresponding author at: Levine Cancer Institute, 1021 Morehead Medical Drive, Suite 100, Charlotte, NC 28204, United States. E-mail address: matthew.ward@atriumhealth.org (M.C. Ward). Oral Oncology 90 (2019) 80–86 1368-8375/ © 2019 Published by Elsevier Ltd. T