Results

As the primary aim of this study was to determine the outcomes for patients with HNSCC who received both nivolumab immunotherapy and radiotherapy, we first identified 76 patients at our institution who had received nivolumab immunotherapy with a diagnosis of platinum resistant recurrent or metastatic HNSCC between February 2018 and August 2020.
On review of their radiotherapy planning records, we identified that among these 76 patients, 16 (21%) had received radiotherapy within two months of a prior dose of nivolumab. The clinical characteristics of the patients who were treated with radiotherapy whilst in receipt of nivolumab are summarised in Table 1. These patients were predominantly male (13/16, 81%), and the median age at diagnosis was 61 (range 48-76 years). Metastatic disease at first presentation was recorded in 19% (3/16), the remainder recurred following previous definitive treatment to localised disease. As primary treatment, 5 (31%) patients had surgery, 5 (31%) had chemoradiotherapy alone and 2 (13%) had radiotherapy alone. Recurrent or metastatic disease developed within less than a year in 5/16 (31%) patients range 2 to 41 months). 5 patients (31%) were given nivolumab as second line systemic therapy following progression within 6 months of prior platinum as part of multi-modality treatment for localised disease. The remainder received nivolumab following progression on platinum based chemotherapy administered in the recurrent or metastatic setting.
The mean duration of nivolumab therapy prior to the initiation of radiotherapy was 16 weeks (range 0 to 43 weeks). On review of the systemic therapy records, of the 16 patients who received radiotherapy within two months of a prior dose of nivolumab, 9 (63%) received further nivolumab subsequent to the radiotherapy and the remainder discontinued nivolumab at that point. The study schematic is shown in Figure 1.
The sites of disease which were irradiated included neck (7/16), abdomen (2), spine (3), and chest (1), skull base (1), oral cavity (1) left maxilla (1). The dose of radiation administered was 8 Gy for 7/16 patients, 20 Gy 5/16, 27.5 Gy 1/16 and 30 Gy for 3/16 patients.
In those that continued with nivolumab subsequent to radiotherapy, two independent clinicians (A.S. and R.M) reviewed the case records of each patient to determine the clinical rationale for radiotherapy alongside nivolumab. For 3/9 patients (33%) radiotherapy was pre-planned alongside the start of nivolumab for symptom control. The indications for symptom control were haemostasis, metastatic cord compression management and pain control. For 5/9 patients (55%), radiotherapy was administered for oligoprogression. For 1/9 patients, radiotherapy was administered to a patient with a very good partial response to the only site of persistent disease.
Durable complete response following radio-immunotherapy was seen in 2 of the 9 patients who continued nivolumab subsequent to radiotherapy. For the first of these patients, previous treatment included concurrent chemo-radiotherapy with Carboplatin for T4N0M0 SCC of the maxilla. Nivolumab was being given for metastatic recurrence and although there was initial response, this patient received radiotherapy to a hilar lymph node which was the only site of progression, after 9 months of nivolumab, when there was radiological response elsewhere. There was a confirmed radiological response to radiotherapy (20 Gy in 5 fractions, Figure 2) and his patient subsequently continued with nivolumab achieving a complete response. At the time of analysis, this patient was alive at 29 months following initiation of nivolumab. The second patient who achieved a durable complete response was initially diagnosed with T3N2M0 SCC of the posterior oropharynx treated with chemoradiotherapy, with recurrence within 6 months of platinum chemoradiotherapy (Figure 3A and 3B). There was a good partial response to nivolumab however, due to persistent clinically evident disease, radiotherapy (30 Gy in 10 fractions) was administered to the oro-mandibular residual disease after 22 weeks of nivolumab (Figure 3C and 3D). There was subsequent complete response clinically (Figure 3E and 3F) and radiologically (Figure 3G and 3H) and the patient is alive at 26 months following start of nivolumab with no evidence of disease.