Abstract

Irene Turturici¹, Giulia Marvaso^1,2, Daniela Alterio¹, Emma D'Ippolito³, Barbara Vischioni⁴, Sara Ronchi⁴, Maria Bonora⁴, Viviana Vitolo⁴, Edoardo Mastella⁵, Giuseppe Magro⁵, Pierfrancesco Franco⁶, Marco Krengli⁷, Piero Fossati⁸, Rosalinda Ricotti⁹, Sara Gandini¹⁰, Stefania Comi¹¹, Anna Maria Camarda¹, Eliana La Rocca¹, Stefania Volpe^1,2, Marta Tagliabue¹², Elena Verri¹³, Ester Orlandi⁴, Barbara Alicja Jereczek-Fossa^1,2, Roberto Orecchia¹⁴

¹IEO European Institute of Oncology IRCCS, Division of Radiation Oncology, Milan, Italy; ²University of Milan, Department of Oncology and Hemato-Oncology, Milan, Italy; ³Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Vision of Radiation Oncology, Napoli, Italy; ⁴Centro Nazionale di Adroterapia Oncologica, Clinical Radiotherapy Unit, Pavia, Italy; ⁵Centro Nazionale di Adroterapia Oncologica, Medical Physics Unit, Pavia, Italy; ⁶University of Turin, Department of Radiation Oncology, Torino, Italy; ⁷University of Piemonte Orientale, Department of Translation Medicine, Radiotherapy Unit, Novara, Italy; ⁸MedAustron Center for Ion Therapy and Research, Medical Department, Wiener, Austria; ⁹Centro Nazionale di Adroterapia Oncologica, Clinical Department-Bioengineering Unit, Pavia, Italy; ¹⁰IEO European Institute of Oncology IRCCS, Epidemiology and Biostatistics Unit, Milan, Italy; ¹¹IEO European Institute of Oncology IRCCS, Unit of Medical Physics, Milan, Italy; ¹²IEO European Institute of Oncology IRCCS, Division of Head and Neck Surgery, Milan, Italy; ¹³IEO European Institute of Oncology IRCCS, Division of Urogenital and Head and Neck Tumors, Milan, Italy; ¹⁴IEO European Institute of Oncology IRCCS, Scientific Directorate, Milan, Italy

To evaluate oncological and toxicity outcome of patients (pts) with locally advanced nasopharyngeal cancer (LANPC) treated with a sequential mixed beam (MB) approach (Intensity Modulated Radiotherapy -IMRT- followed by Proton therapy).

Patients treated with MB (IMRT up to a total dose of 54-60 Gy followed by proton therapy up to a total dose of 70-74 Gy RBE -Relative Biological Effectiveness) between June 2012 to December 2019 were included in the analysis. Clinical outcome (in terms of local control -LC-, -year local relapse free- -LRFS-, distant metastases free- survival -DMFS-) and toxicity profile were evaluated. The Common Terminology Criteria of Adverse Events (CTCAE v4.0) were used for acute and late toxicity reporting.

Forty-six pts with LANPC (cT3-4, N0-N3, M0, according to AJCC 8^th edition) have been analyzed.  All patients underwent concomitant CT. The overall time treatment was of 57 days. After a median follow-up of 34 months, LC was 93% (n=41), 2-year LRFS and DMFS were 92% and 82% respectively. Although stage III represented 50% (n=24) and stage 50% (n=24) of cases, LC control was not statistically different between the two groups (P=0.29 and P=0.95, respectively). No differences were observed between the groups regardless of induction CT (P=0.93 and P=0.47, respectively).

Despite the significantly high doses prescribed in the MB protocol, toxicity profiles were acceptable with events more than Grade 2 equal to 24% (n=11) in the acute and 4% (n=2) in the late toxicity. During RT course five patients out of 46 needed a nutritional support with feeding tube placement, while the majority had Grade 1 weight loss. Considering the remaining acute G3 events, they were dysphagia (4 cases), mucositis (2 cases) and cutaneous toxicity (1 case).

Moreover, clinical outcomes of the MB were compared with those obtained in a retrospective cohort of 17 pts with LANPC treated with only IMRT.  In this group, after a median follow-up of 51 months, LC was 81%, 3-year LRFS and DMFS were 85% and 81%, respectively.

Results showed excellent outcome and acceptable radiation-related side effects in patients treated with a MB approach. Our results are also strengthened by the comparison with the historical group treated with IMRT only. A longer follow-up is required to confirm these promising preliminary results.