Introduction
Head and neck cancer (HNC) is among the most common cancers globally, with approximately 650,000 new cases diagnosed each year.Reference Vigneswaran and Williams1 Despite advances in comprehensive treatment, loco-regional recurrence remains high, occurring in 40–50 per cent of cases.Reference Emami, Borrowdale, Sethi, Thorpe, Chinsky and Small2 Existing salvage treatments offer limited effectiveness and are associated with considerable morbidity.Reference Hartl, Guerlain, Gorphe, Kapre, Kapre Gupta and Saba3
Intra-operative radiotherapy (IORT) is a single dose of radiation that is aimed at a visible tumour bed during surgery. IORT was first developed in Japan in the 1960s and has predominantly been used in head and neck, gastrointestinal, breast and gynaecologic malignancies as part of the wider treatment programme in selected patients.Reference Pilar, Gupta, Ghosh Laskar and Laskar4 There is some evidence of improved survival in this setting.Reference Pilar, Gupta, Ghosh Laskar and Laskar4 There are case series showing the IORT applied in HNC is particularly beneficial in, primary site recurrence, locally advanced primary HNC and post-surgery microscopic disease.Reference Hilal, Al Feghali, Ramia, Abu Gheida, Obeid and Jalbout5
In this report we describe the first UK case of intra-operative electron radiotherapy (IOERT) using a MOBETRON™ in the management of a patient with recurrent squamous cell carcinoma of the head and neck.6 We describe the indications, implementation and procedure.
Case report
In 2015, a 56-year-old lady presented with a four-month history of a left-sided neck mass. Initial investigation with an ultrasound guided needle biopsy of the lymph node demonstrated features suspicious for a carcinoma. The patient underwent a co, puted tmomography (CT) scan showing a left tonsillar mass. Several lung nodules were noted, but these remained stable on interval CT scanning and, therefore, were considered to be reactive. A biopsy of the tonsil taken under general anaesthesia showed a p16 positive staining squamous cell carcinoma (SCC). After discussion with the Head and Neck multidisciplinary team (MDT), the patient received chemoradiotherapy with weekly cisplatin and intensity modulated radiotherapy to the oropharynx and left neck. Following treatment, she remained in remission and under surveillance by the Head and Neck MDT.
Four years later, the patient presented with a suspicious left-sided neck mass confirmed on restaging CT scan as recurrent nodal disease. The previously identified nodules within the lungs were stable. An ultrasound scan and fine needle aspiration could not exclude malignancy. The patient was discussed in the Head and Neck MDT,,,, which recommended a neck dissection with IOERT if indicated.
IOERT pathway at Southampton
New Procedures Advisory Group (NPAG) approval was granted by University Hospital Southampton Clinical governance committees to implement IOERT at Southampton. An IOERT implementation plan was devised by establishing a IOERT Implementation group with standard operating procedures, risks assessment, radiation protection surveys and clinical protocols. Stage 1 was a didactic educational training session for the whole team. IORT training packages were completed, including site visits by the lead head and neck oncologist, radiographers and radiotherapy physicists. A simulation training session was performed with a mannequin followed by a mock training exercise was performed with a volunteer wherein all the steps of MOBETRON™ positioning and theatre ergonomics flow (Fig. 1) were tested (Fig. 2).
Pre-operative and operative MOBETRON™ stages.
(A) MOBETRON™ device setup in theatre. (B) MOBETRON™ setup and cone alignment on example patient.
A left modified neck dissection was undertaken with intra-operative frozen sections confirming SCC. The patient then received IORT via the MOBETRON™, delivering 10 Gy single fraction with 6 MeV energy chosen after review of intra-operative findings and radiotherapy depth dose chart measurements.
The final histology confirmed the excised left neck lymph node was positive for metastatic SCC. The patient recovered well after her surgical procedure with no significant sequalae. The patient was subsequently closely monitored by the Head and Neck MDT over a further three years and had no evidence of locoregional recurrence. The patient had no post-operative complications, specifically, no neurological symptoms, fibrosis or evidence of vascular compromise and maintained her quality of life.
Discussion
The IORT/IOERT delivery system is based on the principle of directing a focused beam of radiotherapy to a visible tumour bed. The benefit of such approach is two-fold, the first being the increased accuracy and predictability of delivery and secondly the reduced collateral exposure to healthy surrounding tissue in comparison to traditional external beam radiotherapy (EBRT).
In several studies, IORT is reported to have a low complication rate; the patient described here did not suffer from late complications of IORT. Pinheiro et al (2002) reported IORT as an adjuvant therapy in advanced HNC and skull base cancer. A total of 44 patients with HNC were included: 34 had SCC and 10 had non-SCC. IORT dose in the range of 12.5 Gy to 22.5 Gy was delivered, and complications only occurred in one patient who received an increased dose of radiotherapy at 22.5 Gy.Reference Pinheiro, Foote, McCaffrey, Kasperbauer, Bonner and Olsen7
IORT reduces the hospital stay and costs to the hospital in comparison to brachytherapy where the patient remains in hospital for the duration of post-operative treatment.Reference Chargari, Deutsch, Blanchard, Gouy, Martelli and Guérin8 IORT can deliver a single dose of radiotherapy that is two to three times higher than EBRT to a defined area with no significant late toxicities typically associated with standard EBRT. This higher dose of IORT would potentially allow dose reduction of EBRT when used in combination with IORT, thus, potentially reducing overall radiotherapy associated late toxicity.Reference Kyrgias, Hajiioannou, Tolia, Kouloulias, Lachanas and Skoulakis9
The introduction of IORT requires significant investment in capital, infrastructure and staffing (see Fig. 1). Resources need to be allocated to radiotherapy planning as IOERT offers new challenges compared with conventional radiotherapy. Theatre redesign needs to occur and dose exposure needs to be considered in scheduling cases. Safety is paramount and includes consideration of radiation protection, use of the novel equipment and remote anaesthesia. The IOERT implementation process at our centre involved setting up lead IOERT team, formulation of standard operating procedures, radiation protection surveys, governance framework approvals, clinical protocols and several training sessions. For the wider MDT team. The introduction of such a service, therefore, requires a significant number of resources.
Conclusion
We have described the first UK case of a patient with recurrent SCC of the tonsil with MOBETRON™ IOERT as an adjuvant therapy to surgical salvage. The patient remained disease free over three years with no treatment sequelae. IORT/IOERT for adjuvant treatment to surgical salvage for recurrent HNC may offer improved locoregional control and survival, with reduced toxicity and better quality of life. Further prospective trials are necessary to evaluate treatment benefit, complication profile, optimal protocols, logistics of delivery, quality-adjusted life-years (QALYs) and health economic analysis.
Acknowledgements
Many thanks to Dr Fiona Penny who contributed extensively to the writing of this report which has now been re-written and edited.
Financial support
The authors declare none.
Competing interests
The authors declare none.
Ethical standards
Approval was obtained via the New Procedures Advisory Group (NPAG) at University Hospital Southampton.
