Re-irradiation with concurrent and maintenance nivolumab in locally recurrent and inoperable squamous cell carcinoma of the head and neck: A single-center cohort study

Alev Altay-Langguth; Panagiotis Balermpas; Christian Brandts; Sven Balster; Shahram Ghanaati; Ria Winkelmann; Iris Burck; Franz Rödel; Daniel Martin; Claus Rödel; Jens von der Grün

doi:10.1016/j.ctro.2021.03.004

Re-irradiation with concurrent and maintenance nivolumab in locally recurrent and inoperable squamous cell carcinoma of the head and neck: A single-center cohort study

Clin Transl Radiat Oncol. 2021 Mar 26:28:71-78. doi: 10.1016/j.ctro.2021.03.004. eCollection 2021 May.

Authors

Alev Altay-Langguth¹, Panagiotis Balermpas^{1

2}, Christian Brandts^{3

4

5}, Sven Balster⁶, Shahram Ghanaati⁷, Ria Winkelmann⁸, Iris Burck⁹, Franz Rödel^{1

4

5}, Daniel Martin^{1

4

5}, Claus Rödel^{1

4

5}, Jens von der Grün^{1

4}

Affiliations

¹ Department of Radiotherapy and Oncology, University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
² Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
³ Department of Medicine, Hematology and Oncology, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany.
⁴ German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg and German Cancer Consortium (DKTK), Partner Site Frankfurt am Main/Mainz, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁵ Frankfurt Cancer Institute (FCI), University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁶ Department of Otorhinolaryngology, University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁷ Department of Oral, Maxillofacial and Facial Plastic Surgery, University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁸ Senckenberg Institute of Pathology, University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁹ Department of Diagnostic and Interventional Radiology, University Hospital, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Abstract

Background: The rate of loco-regional recurrences for locally advanced head and neck squamous cell carcinoma (HNSCC) following standard treatment reaches up to 50%, accompanied by a probability of 20% to develop a second primary tumor in the head and neck region.

Methods: Ten patients with inoperable, in-field recurrence of HNSCC following previous primary or adjuvant radiotherapy (RT) in combination with concurrent platinum-based chemotherapy were re-irradiated with 60 Gray in 30 fractions between December 2017 and January 2020 with concurrent and maintenance nivolumab administration. Data were retrospectively collected and compared with patients who underwent re-irradiation (ReRT) with concurrent cisplatin following propensity score matching (PSM). Local progression-free survival (LPFS) and overall survival (OS) were visualized using Kaplan-Meier method (log-rank test).

Results: All patients completed ReRT. Median number of applied courses of nivolumab was 12 (range, 3-38). OS rate was 50% at 12 months and the median OS was 11 (range, 2-23) months. Six and 12 month LPFS rates were 60% and 30%, respectively. Median LPFS was 8 (range, 2-19) months. OS and LPFS rates were not inferior to those of patients treated with concurrent cisplatin. No unexpected radiation-related toxicity occurred. A total of four patients developed any-grade immune-related adverse events of which two presented with grade 3 toxicities. One patient died within 3 weeks after ReRT. Higher blood levels of CRP (p = 0.004), lower levels of hemoglobin (p = 0.029) and higher neutrophil/lymphocyte ratio (p = 0.004) were associated with impaired LPFS. Higher recursive portioning analysis (RPA) class was associated with impaired LPFS (p = 0.022) and OS (p = 0.024).

Conclusion: The combination of ReRT and nivolumab for locally recurrent HNSCC was feasible without occurrence of unexpected toxicities. Combined radioimmunotherapy might offer an effective treatment option for carefully selected pre-irradiated patients ineligible for salvage surgery.

Keywords: Head and neck cancer; Immunotherapy; Nivolumab; Radiotherapy; Re-irradiation.