Abstract
Background: During the COVID-19 pandemic, pedicle flaps instead of free flap transfer were recommended for head and neck reconstruction to reduce infection risk. Boron neutron-capture therapy in Japan was clinically approved in 2020 as a salvage radiotherapy for recurrent head and neck cancer following chemoradiotherapy. The efficacy and safety of salvage surgery following boron neutron-capture therapy remain unclear. Case Report: We describe a 57-year-old male with crT4aN0M0 oral cancer after three different forms of radiotherapy including boron neutron-capture therapy, treated by salvage partial maxillectomy with both buccal fat pad and nasoseptal flaps. His postsurgical course was successful, without tracheostomy, and he had no Clavien– Dindo grade 3 or 4 complications. The pathological diagnosis was T4a squamous cell carcinoma with a negative surgical margin. No recurrence or metastasis had occurred at 113 days postoperatively. No opioid consumption was needed postoperatively. Conclusion: Pathological negative margins were achieved in this case and there were no severe complications. Further accrual of cases salvage surgery following boron neutron-capture therapy is required to clarify treatment strategies for recurrent head and neck cancer.
Reducing tracheostomy or free flap transplantation during the coronavirus disease 2019 (COVID-19) pandemic was recommended to reduce the risk of infection in the surgical management of head and neck cancer (HNC) (1). Boron neutron-capture therapy (BNCT), using a combination of a neutron beam and a boron drug, has been clinically available in Japan for patients with unresectable recurrent tumor following radiotherapy (RT) or chemoradiotherapy (CRT) for HNC from 2020 (2-4). Because the complete response rate of recurrent HNC to BNCT is approximately 30-50% (2), an increase in patients with recurrent tumor following BNCT may be expected. To the best of our knowledge, salvage surgery for recurrent tumors following BNCT is mostly undertaken for brain tumors (5). Here, we describe a patient who was treated by salvage surgery for recurrent squamous cell carcinoma (SCC) following BNCT in HNC during the COVID-19 pandemic.
Case Report
This case report, presented according to the Declaration of Helsinki, was approved by the Review Board of Aichi Cancer Center (receipt number: 2021-0-118). A 57-year-old man with growing recurrent SCC in the upper gum was referred to our hospital. His past history of gingival SCC indicated that he had undergone three different RT courses as well as various chemotherapies. Conventional RT at a total dose of 40 Gy in 20 fractions using platinum-based intra-arterial chemotherapy was the initial definitive therapy administered when he was 46 years old. BNCT of the tumor at both the maximum dose of 40-Gy equivalent and the minimum dose of 20-Gy equivalent in one fraction with 500 mg/kg boronophenylalanine was used as the salvage therapy for recurrent tumor when he was 53 years old. Stereotactic body RT at both the maximum dose of 61.4 Gy and the peripheral dose of 35 Gy in seven fractions was used as resalvage therapy for recurrent tumor at 54 years old. Chemotherapies were docetaxel hydrate, nedaplatin, paclitaxel, cetuximab, carboplatin, 5-fluorouracil, nivolumab and pembrolizumab. Figure 1 shows the planning computed tomography (CT) for the three different RTs and the dose– volume histogram of the BNCT.
Planning computed tomography for upper gingival cancer at initial therapy with conventional radiotherapy (A), at salvage therapy with boron neutron-capture therapy (B), at re-salvage therapy with stereotactic body radiation therapy (C). Dose–volume histogram for boron neutron-capture therapy (D).
Palpation and visual inspection including nasopharyngoscopy at our hospital revealed a gingival tumor, without eye symptoms. Subsequently, an enhanced CT and magnetic resonance imaging showed a maximum diameter of 4.7 cm of the tumor involving the right maxillary sinus. Both enhanced whole-body CT and 18F-fluorodeoxyglucose positron-emission tomography with CT detected no metastases for regional or distant sites. Biopsy specimens from the gingival tumor were pathologically confirmed as SCC. The patient’s diagnosis was T4aN0M0 upper gingival SCC as categorized in the eighth edition of the classification by the Union for International Cancer Control. Figure 2 shows the patient’s presurgical images.
Preoperative images of upper gingival cancer. A: White light endoscopy. B: Enhanced computed tomography. C: Enhanced magnetic resonance. D: 18F-Fluorodeoxyglucose positron-emission tomography with computed tomography.
After a multidisciplinary conference, partial maxillectomy with preservation of the orbital floor in an en bloc fashion was recommended as definitive salvage treatment for the patient. Preoperative opioid prescribed for cancer-related pain was oxycodone hydrochloride hydrate at 10 mg/day. Postsurgical reconstruction for the surgical defect was planned using both surgical obturator and pedicle flap, such as the buccal fad pad, nasoseptal, and supraclavicular artery. His presurgical antigen test for COVID-19 was negative.
The gingival tumor was resected under general anesthesia by partial maxillectomy with both preservation of both eyeballs and careful ligation of the vessels such as the branches of the maxillary artery. The resultant defect, which was a open pharyngeal wound between the nasal/paranasal mucosa and pharyngeal mucosa, was difficult to cover with only a flap comprising a buccal fat pad measuring approximately 2×2 cm. The remaining open wound was covered without tension by a nasoseptal flap measuring approximately 3×5 cm from the pedicle of the sphenopalatine artery with preservation of the olfactory cleft. After the pharyngeal reconstruction, following both face suture and nasal packing, the surgical obturator was placed.
The patient was extubated in the surgical room immediately. The nasal packing was removed on the fifth postoperative day (POD). The nasogastric tube was decannulated on the 14th POD following oral intake recovery, and the patient was discharged on the 18th POD. The resected specimen, with a maximum diameter of 4 cm and was pathologically diagnosed as T4a upper gingival SCC invading the maxillary sinus with tumor-negative margins. Figure 3 shows the surgical and pathological images.
Images of upper gingival cancer at salvage surgery. A: Skin incision line. B: Surgical specimen. C: Sutured buccal fat pad and nasoseptal flaps. D: Hematoxylin and eosin staining of the gingival specimen (×20).
On the 113th POD, no recurrence or metastasis was found by whole-body enhanced CT and nasoparyngoscopy (Figure 4). His clinical course had no Clavien–Dindo grade 3 or 4 postsurgical complications such as flap necrosis. No opioids for pain were needed after surgery.
White light endoscopy (A) and enhanced computed tomography (B) at 4 months after salvage surgery.
Discussion
Salvage surgery, a classical definitive therapy for recurrent HNC, remains a challenging therapy following RT with various combination therapies for SCC due to postsurgical complications (6). We also showed postsurgical courses following carbon-ion RT (7), platinum-based CRT, and cetuximab-based bioRT in HNC (8) with Clavien–Dindo scoring. There were two serious complications in 11 patients who underwent salvage maxillectomy following intra-arterial cisplatin-based CRT, with deep vein thrombosis in one and local infection sepsis in the other, but those patients did not undergo BNCT (9). Therefore, the safety of salvage maxillectomy following BNCT remains unclear.
BNCT as a next-generation form of RT has a high-dose concentration for nuclear reaction with boron in malignant tumor, as well as causing less damage to normal tissues (2). A phase II trial of BNCT for 29 cases with HNC reported eight cases with recurrent or unresectable non-SCC and no cases with recurrent SCC underwent salvage surgery following BNCT during the survival follow-up period (4). Postsurgical complications for salvage surgery following BNCT in the trial were not described (4). Therefore, we believe that further accumulation of cases of salvage surgery following BNCT for recurrent SCC in HNC are needed.
Defects following maxillectomy are reconstructed by various flaps with/without surgical obturators (10). A review of 1,635 cases with a buccal fat pad flap showed a success rate of 96.2% (11), and a meta-analysis of 27 articles on nasoseptal flap reported a necrosis rate of 0-1.3% (12). We selected use of both a buccal fat pad and nasoseptal flaps due to safety and the reduction of medical resources, such as those needed under free-flap transplantation with tracheostomy, during the COVID-19 pandemic. Indeed, this case had no Clavien–Dindo grade 3-4 postsurgical complications as reported previously (11, 12).
In conclusion, we demonstrated that a patient who underwent salvage maxillectomy with pathological negative margin following BNCT for recurrent oral SCC during the COVID-19 pandemic had neither recurrent tumor nor Clavien–Dindo grade 3-4 postsurgical complications up to 4 months post surgery. Accumulation of cases of salvage surgery following BNCT is needed to further the development of next-generation RT.
Acknowledgements
This case report was supported by the Japan Society for the Promotion Science KAKENHI (Grant number: 21K09575).
Footnotes
Authors’ Contributions
HS was the main surgeon and wrote the original draft. MY, SH, YK and SI assisted in the surgery. ES acquired pathological images. DN, SB, HT, MS and NH reviewed the case report.
Conflicts of Interest
All Authors declare no conflicts of interest.
- Received January 20, 2022.
- Revision received February 4, 2022.
- Accepted February 7, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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