The Laryngoscope V C 2012 The American Laryngological, Rhinological and Otological Society, Inc. Toxicity, Quality of Life, and Functional Outcomes of 176 Hypopharyngeal Cancer Patients Treated By (Chemo)Radiation: The Impact of Treatment Modality and Radiation Technique Abrahim Al-Mamgani, MD, PhD; Robert Mehilal, MD; Peter H. van Rooij, MSc; Lisa Tans, MD; Aniel Sewnaik, MD, PhD; Peter C. Levendag, MD, PhD Objectives/Hypothesis: The main goal of the current study was to comprehensively address the impact of chemoradia- tion and radiation techniques on toxicity, quality of life (QoL), and functional outcome. Study Design: Retrospective analysis of toxicity and functional outcome and prospective QoL assessment. Methods: From 1996 to 2010, 176 consecutive patients with hypopharyngeal cancer (HPC) were treated with (chemo)- radiotherapy. End points were acute and late toxicity, QoL assessment, and functional outcome using laryngoesophageal dys- function-free survival (LED-FS) defined by the Laryngeal Preservation Consensus Panel. Results: Chemoradiation significantly increased grade 3 acute toxicity compared to radiotherapy alone (71% vs. 55%, P ¼ .02). The 3-year grade 2 late toxicity was 32%. Intensity-modulated radiotherapy (IMRT) significantly reduced late tox- icity compared to three-dimensional conformal radiotherapy (3DCRT) (24% vs. 44%, P ¼ .007). Slight deterioration in QoL scores was observed on almost all scales, and was more pronounced in patients treated with chemoradiation, albeit not stat- istically significant except for xerostomia. Chemoradiation, compared to radiotherapy alone, improved LED-FS at 3 years (51% vs. 24% for the entire group and 83% vs. 63% for the 78 living patients at last follow-up, respectively [P ¼ .05]). Conclusions: Compared to radiotherapy alone, chemoradiation significantly improved functional outcome, increased acute toxicity, but without significant increase in late radiation-induced side effects. Statistically significant deterioration in QoL scores was reported only for xerostomia. IMRT, compared to 3DCRT, reduced the incidence and severity of acute and late toxicity, thereby broadening the therapeutic window, and may allow dose escalation for further improvement of outcomes of laryngeal preservation protocols. Key Words: Head and neck, radiation therapy, quality of life, chemotherapy, hypopharynx. Level of Evidence: 2c. Laryngoscope, 122:1789–1795, 2012 INTRODUCTION In addition to curing, the goals of treatment of hypo- pharyngeal cancer (HPC) should include laryngeal preservation while minimizing side effects. Early-stage dis- ease can be treated effectively with a single-modality larynx-sparing approach, whereas total laryngectomy (TLE) followed by postoperative radiotherapy (PORT) might be the best option to achieve local control in locally advanced dis- ease. However, because of the importance of the larynx for speech and swallowing functions, patients with T3 and early T4 should be offered the possibility of organ preservation with chemoradiation (CRT), unless explicitly contraindi- cated. In different studies, this treatment approach has resulted in good oncologic outcomes, similar to those achieved by TLE and PORT but with high rates of treat- ment-related toxicity. 1,2 Most studies addressing these treatment modalities focus on oncologic outcomes, whereas rates of treatment-related toxicities and assessment of qual- ity of life (QoL) are inconsistently reported. The standard laryngeal preservation treatment schedule for HPC at our institution consists of definitive radiotherapy (RT) for T1 and T2, and CRT for T3 and most patients with T4a, where an attempt at laryngeal preservation was regarded as realistic as judged by the head and neck surgeons during the weekly multidiscipli- nary meeting. Other patients with T4a and all T4b patients where considered at advanced stage. In these patients, TLE 6 neck dissection followed by PORT was advocated. When surgery was not possible because of comorbidity or the patient’s refusal, RT with or without chemotherapy was given to these patients. The main goals of our study were to retrospectively review the toxicity and functional outcomes of laryngeal preservation treatment protocol for HPC in our center, to identify clinical factors predicting feeding tube depend- ency, and to prospectively analyze the impact on QoL. From the Department of Radiation Oncology (A.A.-M., R.M., L.T., P .C.L.), Department of Biostatistics (P .H.V .R.), Department of Otorhinolaryngology (A.S.), Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands. Editor’s Note: This Manuscript was accepted for publication April 5, 2012. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Abrahim Al-Mamgani, MD, PhD, Depart- ment of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Cen- ter, Groene Hilledijk 301, 3075 EA, Rotterdam, the Netherlands. E-mail: a.al-mamgani@erasmusmc.nl DOI: 10.1002/lary.23387 Laryngoscope 122: August 2012 Al-Mamgani et al.: Outcome After CRT for Hypopharyngeal Cancer 1789