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.