Lemierre's Syndrome after Head and Neck Photoimmunotherapy for Local Recurrence of Nasopharyngeal Carcinoma.

Introduction: Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre's syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre's syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma. Case Presentation: A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy. Three months after HN-PIT, the patient developed fever and neck pain, which led to a diagnosis of Lemierre's syndrome. The patient was treated with antibiotics and anticoagulants for at least 1 month. The patient's general condition and inflammatory findings on blood sampling showed gradual improvement, and a follow-up cervicothoracic computed tomography imaging showed that the venous thrombus had been obscured and the patient was doing well. Conclusion: HN-PIT is a high-risk procedure for the development of Lemierre's syndrome due to irradiation-induced mucositis, and anticipating the development of Lemierre's syndrome during HN-PIT is important.

Two Cases of Emergency Tracheostomy After Head and Neck Photoimmunotherapy.

Background/Aim: Head and neck photoimmuno-therapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023. Of these, we experienced two cases in which preventive tracheostomy was not performed because the risk of laryngeal edema was considered low; however, laryngeal edema developed after treatment, and an emergency tracheostomy had to be performed. Case Report: Case 1 was a patient in his 70s with a local recurrence of mandibular gingival carcinoma. HN-PIT using cylindrical diffusers was performed on the target lesion, extending from the lateral wall of the oropharynx to the soft palate. Case 2 was also a patient in his 70s with carcinoma of the mid-pharynx. HN-PIT was performed using a frontal diffuser to target lesions extending from the soft palate to the buccal mucosa. Notably, both patients developed laryngeal edema after HN-PIT, and an emergency tracheostomy had to be performed. Conclusion: HN-PIT treatment is still being established through a trial-and-error method and is still incomplete.

A Case of Successful Treatment with an Immune Checkpoint Inhibitor after Head and Neck Photoimmunotherapy.

Introduction: Head and neck photoimmunotherapy (HN-PIT) has been conditionally approved by the Japanese government for the treatment of unresectable locally advanced or locally recurrent head and neck cancer since January 2021. HN-PIT makes local treatment of locally recurrent disease possible in cases where systemic drug therapy would have previously been the only option. However, when treatment is ineffective and the disease progresses, it is necessary to shift to conventional drug therapies. We report a case in which an immune checkpoint inhibitor (ICI) was successfully administered to a patient with advanced disease following HN-PIT. Case Presentation: A 75-year-old male patient presented with local recurrence of mandibular gingival cancer. The primary treatment consisted of mandibular segmentectomy and reconstruction with a scapulohumeral and vastus lateralis skin valve. Post-operative radiotherapy was administered. Local recurrence was found in the mid-pharynx adjacent to the reconstruction. HN-PIT was performed for the local recurrence. After three cycles of HN-PIT, the local lesion increased, and the disease was evaluated as advanced. Therefore, the patient was switched to pembrolizumab, an ICI. Conclusion: The recurrent lesions disappeared 2 months after the first dose of pembrolizumab, and the patient remained in clinical remission at 1 year. To the best of our knowledge, there are no other reports of successful ICI therapy after HN-PIT.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

A Case of Oropharyngeal Carcinoma with an Oblique Neck that Benefited from Transoral Robotic Surgery.

Transoral robotic surgery (TORS) and transoral videolaryngoscopic surgery (TOVS) are minimally invasive procedures for early-stage head and neck cancers. However, due to its unique nature, transoral resection often leads to skeletal and anatomical disorders. We describe a case in which TORS was used in a 71-year-old man with a skeletal disorder, spastic stridor, and a T2N1M0 stage I p16-positive oropharyngeal carcinoma. Prior to the procedure, he underwent right cervical dissection (levels II-IV). Although he had an oblique neck, the right side of his neck was naturally hyperextended because the dissection was performed on the right side. The right facial, lingual, and external carotid arteries were ligated in preparation for TORS. Postoperative pathological examination revealed no extranodal involvement of the metastatic lymph nodes. A two-stage TOVS procedure was performed for the oropharyngeal tumor, in which the surgeon was required to be positioned at the patient's head to allow direct manipulation. This makes the neck and oral cavity more susceptible to the skeletal effects. In contrast, in TORS, the da Vinci insertion angle can be set to match the angle of the neck, allowing surgeons to operate with less skeletal influence. TORS is more useful in this setting.

Postoperative Pharyngeal Fistula Diagnosed by Prone Position Computed Tomography With Oral Contrast Agent: A Case Report.

BACKGROUND/AIM: A pharyngeal fistula is the most common complication of total laryngectomy; thus, accurate diagnosis and treatment are important. Diagnosis is usually made by the finding of leakage of the contrast agent outside the pharynx during swallowing contrast examination. Herein, we encountered a case in which fine leaks not detected on contrast examination during swallowing were visualized and diagnosed by computed tomography (CT) imaging with oral contrast media with the patient in a prone position. CASE REPORT: During imaging in a prone position, the contrast agent entered the sutures on the cephalocaudal and ventral sides of the surgical site, which were particularly prone to leaks due to gravity, and it was possible to diagnose minute leaks. When there is a high risk of postoperative pharyngeal fistula, such as in reconstructive cases with a pedunculated flap or with overlapping risk factors such as preoperative irradiation, CT imaging with contrast medium in a prone position is considered useful when swallowing contrast examination does not provide a clear diagnosis. However, suture failure is possible, and this should be evaluated. CONCLUSION: This case suggests that routine prone CT may lead to the early detection of postoperative pharyngeal fistula in high-risk cases. Further accumulation of cases is required to confirm our findings.

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC). PATIENTS AND METHODS: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases. RESULTS: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively. CONCLUSION: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future.

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study.

BACKGROUND/AIM: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities. PATIENTS AND METHODS: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared. RESULTS: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02). CONCLUSION: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors.

Nivolumab for Platinum-refractory and -sensitive Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Nivolumab has antitumor efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who relapse within 6 months after platinum-based therapy; however, the efficacy of nivolumab for platinum-sensitive R/M HNSCC has not been shown. Therefore, this study compared the efficacy and safety of nivolumab for platinum-refractory and platinum-sensitive R/M HNSCC. PATIENTS AND METHODS: This was a retrospective study of patients who received nivolumab for R/M HNSCC who had been previously treated with platinum-based anticancer drugs. Patients were divided into a platinum-sensitive and a platinum-refractory group, and progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) [complete response (CR) + partial response (PR)], the disease control rate (DCR) (CR + PR + stable disease), and the incidence of immune-related adverse events (irAEs) were compared between the two groups. RESULTS: We included 88 patients with squamous cell carcinoma: 60 with platinum-refractory disease and 28 with platinum-sensitive disease. The median PFS in the platinum-refractory and platinum-sensitive groups were 2.7 months and 5.3 months, respectively (p=0.03), and the median OS were 8.8 months and 17.1 months, respectively (p=0.06). There were no significant differences in the ORR, DCR, or incidence of irAEs between the two groups (p>0.99, p=0.11, and p>0.99, respectively). CONCLUSION: Nivolumab is a safe and effective treatment for platinum-sensitive R/M HNSCC.

Quality-of-Life Evaluation of Patients with Unresectable Locally Advanced or Locally Recurrent Head and Neck Carcinoma Treated with Head and Neck Photoimmunotherapy.

Head and neck photoimmunotherapy (HN-PIT), a new treatment developed for local control of head and neck carcinoma, uses cetuximab sarotalocan sodium with a laser system to specifically destroy only tumor cells. No studies have examined the impact of HN-PIT on the quality of life (QOL) of patients with head and neck cancer. This study assessed the QOL of patients with unresectable locally advanced or locally recurrent head and neck carcinoma (LA/LR-HNC) treated with HN-PIT. Nine eligible patients with unresectable LA/LR-HNC who underwent HN-PIT at our institution between 20 January 2021 and 30 April 2022 were included in the study. They completed a QOL evaluation form. The primary endpoint was QOL assessment. The secondary endpoints were overall response rate, overall survival (OS), progression-free survival, and adverse events. QOL was compared before and 4 weeks after HN-PIT. There were no significant changes in all QOL assessment parameters after treatment with HN-PIT. The overall response rate was 89%, and safety was acceptable. For patients with unresectable LA/LR-HNC, HN-PIT provided good local control without decreasing the QOL. The addition of HN-PIT to conventional head and neck carcinoma treatment may lead to the prolongation of OS in head and neck carcinoma.

Real-world treatment patterns and outcomes in Japanese patients with cervical esophageal cancer.

BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

Postoperative Complications and Swallowing Function after Jejunal and Skin Flap Reconstruction for Hypopharyngeal Carcinoma-A Multicenter Retrospective Study.

This study compared the incidence of perioperative complications and swallowing function between free jejunal flap reconstruction and cutaneous free tissue flap construction. We included 223 patients who underwent hypopharyngeal reconstruction using free flap. At discharge, +the free jejunal flap was associated with a Functional Oral Intake Scale (FOIS) score of 1-6 in 132 cases (70%) and a score of 7 in 56 cases (30%). Regarding the cutaneous free tissue flaps, FOIS scores of 1-6 were observed in 18 cases (51%), and a score of 7 was noted in 17 cases (49%). Donor site complications occurred in 12% of the patients who underwent free jejunal flap procedures and in none of the patients who underwent cutaneous free tissue flap procedures. We found that the free jejunal flap had a regular dietary intake rate in 56 patients (30%), whereas cutaneous free tissue flaps had a regular dietary intake rate in 17 patients (49%). Cutaneous free tissue flaps had a significantly higher regular dietary intake rate at discharge and a significantly lower incidence of donor site complications than free jejunal flaps. In conclusion, free-flap reconstruction may be a better method than free jejunal flap reconstruction for the treatment of hypopharyngeal cancer.

A Case Treated With Photoimmunotherapy Under a Navigation System for Recurrent Lesions of the Lateral Pterygoid Muscle.

BACKGROUND: Head and neck photoimmunotherapy specifically destroys tumor cells by irradiating them with 690 nm red light after administering cetuximab sarotalocan sodium. The key point in the technique of photoimmunotherapy is to set the irradiation area precisely with a margin added to the target lesion while securing a safety zone with large vessels such as the internal carotid artery. CASE REPORT: At our Institution, we performed photoimmunotherapy in combination with use of a navigation system on a male patient in his 70s with maxillary gingival carcinoma who had a recurrent lesion deep in the lateral pterygoid muscle. Three months after photoimmunotherapy, the superficial lesion had disappeared, the area of contrast within the lateral pterygoid muscle had improved, and the patient was deemed to have a complete response. CONCLUSION: The Navigation System was successfully used in combination with photoimmunotherapy. Additionally, this allowed the location of the internal carotid artery to be confirmed in real time.

A Case of Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab.

BACKGROUND: No clear chemotherapy regimen for recurrent or metastatic parotid cancer exists. We describe our experience with pembrolizumab to treat recurrent or metastatic parotid cancer. CASE REPORT: A 73-year-old woman with swelling in the lower part of the right ear for 10 years before surgery was diagnosed with right parotid cancer, underwent total right parotidectomy, and reported recurrence. She requested treatment due to diminished quality of life caused by neurological symptoms. Tissue was collected from the recurrent lesion and its combined positive score was >20; pembrolizumab was started 9 years postoperatively. RESULTS: To date, the patient has received 14 cycles of pembrolizumab. Evaluation by computed tomography showed a partial response to treatment. The only immune-related adverse event was grade 1 pneumonia in both lungs. CONCLUSION: Significant response to pembrolizumab in recurrent or metastatic parotid cancer is rarely reported, making this a remarkable case. We plan to continue pembrolizumab administration.

PD-L1 Expression and Survival Rates Using TPS and CPS for Nivolumab-treated Head-and-Neck Cancer.

BACKGROUND/AIM: This study investigated the expression and survival rates of programmed cell death ligand 1 using the tumor proportion score (TPS)and combined positive score (CPS) for recurrent/metastatic head and neck cancer administered nivolumab. PATIENTS AND METHODS: Forty-seven patients with recurrent/metastatic head and neck cancer with a history of platinum-based chemotherapy who received nivolumab between June 1st, 2017, and January 31st, 2019 were included in this study. RESULTS: TPS and CPS were strongly correlated (r=0.546). When the TPS was high (≥40%), overall and progression-free survival were significantly better. The median overall survival was 8.5 months, median progression-free survival was not reached, and the 1-year progression-free survival rate was 71.4%. However, there was no significant difference in overall and progression-free survival between the groups with high CPS (≥20). CONCLUSION: This is the first report to show a strong correlation between TPS and CPS. High TPS (40% or higher) may be used as a predictor of prognosis and efficacy. Further studies are warranted to determine the use of the CPS as a biomarker.

Comparison of Dosage of Nivolumab in Efficacy and Safety for Recurrent Metastatic Squamous Cell Carcinoma.

BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.

Photoimmunotherapy for Managing Recurrent Laryngeal Cancer Cervical Lesions: A Case Report.

Photoimmunotherapy (PIT) targets and destroys tumor cells through irradiation with 690-nm red light after the administration of cetuximab sarotalocan sodium, which contains IRDye700DX bound to cetuximab. In Japan, PIT is a new treatment that is covered by insurance only for unresectable head and neck cancers. However, this treatment has conditional early approval. There have been no case reports describing the efficacy of this treatment in a real-world setting thus far. We report our experience with PIT for head and neck cancer. A 76-year-old man with laryngeal cancer underwent radiation therapy and surgery. Skin involvement in the right submandibular region was subsequently noted. We diagnosed local recurrence and performed PIT for this lesion. Partial response was achieved after the first PIT session, and progressive disease was diagnosed after the second session. Many aspects of PIT remain unclear and should, therefore, be clarified in further research. Despite this uncertainty, PIT may become an effective treatment strategy for head and neck cancer if the patient selection criteria are delineated.

Pericardial metastasis of parotid mucoepidermoid carcinoma diagnosed by pericardial biopsy.

A 30-year-old man presented with swelling in the lower left ear. Close examination led to a diagnosis of parotid gland cancer, T4N0M0 Stage IVA, so total resection of the left parotid gland and left neck dissection were performed. Pathological examination led to a diagnosis of high-grade malignant-type mucoepidermoid, and chemoradiotherapy was performed as postoperative treatment. Fourteen days after completion of chemoradiotherapy, the patient was admitted to the hospital with headache and lack of appetite. Echocardiography showed a pericardial effusion and complete collapse of the right ventricle; cardiac tamponade was diagnosed, and pericardiocentesis was performed. The pericardial effusion was bloody, and a metastatic lesion was suspected, but cytological examination showed class IIIa. On day 33 of the illness, respiratory distress and hypotension were observed. A clot was seen covering the lower wall of the heart, and dilatation of the lower wall was significantly impaired. Pericardiotomy was performed on day 36. Pathological examination diagnosed cardiac metastasis of mucoepidermoid carcinoma of the parotid gland. Although only 4 cases of parotid cancer have been reported as primary lesions of metastatic heart tumors, this case represents the world's first description of isolated parenchymal metastasis of mucoepidermoid carcinoma of the parotid gland diagnosed by pericardial biopsy.

Effect of Concomitant Lafutidine on Adjuvant S-1 for Head and Neck Cancer: A Comparative Study.

BACKGROUND/AIM: This study evaluated the utility of the histamine H2-receptor antagonist lafutidine in patients taking oral fluorouracil (S-1) for head and neck squamous cell carcinoma (HNSCC), by comparing patients with and without concomitant lafutidine. PATIENTS AND METHODS: Study subjects comprised 63 patients who received adjuvant S-1 following curative resection of HNSCC at our institutions between August 1, 2013 and December 31, 2019. The primary endpoint was the completion rate of S-1 therapy. RESULTS: For the lafutidine-treated group, the median completion rate was significantly greater (94.4% vs. 24.6%, p=0.01), and progression-free and overall survival were both significantly prolonged compared to the non-lafutidine group. In terms of adverse events, the incidence of diarrhoea was significantly reduced (p<0.00189) in the lafutidine-treated group. CONCLUSION: Taking lafutidine during S-1 treatment appeared to reduce gastrointestinal disturbance and increased the S-1 completion rate, improving both progression-free and overall survival as a result.

Postoperative Complications of Jejunal and Skin Valve Reconstruction in Free Reconstructive Surgery for Hypopharyngeal Carcinoma.

BACKGROUND/AIM: This study evaluated the incidence of perioperative complications in jejunal flap compared with the free tissue flap approach. PATIENTS AND METHODS: This study included 75 patients who underwent free flap reconstruction for hypopharyngeal carcinoma. The primary outcome was the incidence of pharyngocutaneous fistula, and the secondary outcomes were perioperative complications. RESULTS: Pharyngocutaneous fistula developed in 7% of patients who underwent jejunal flap procedures and 6% of patients who underwent free tissue flap procedure. Flap sampling site complications occurred in 23% of patients who underwent jejunal flap procedures and in none of the patients who underwent free tissue flap procedure. CONCLUSION: No significant difference was observed in the incidence of pharyngocutaneous fistula between the two groups (p=0.99), but complications at the flap sampling site were significantly more common in jejunal flap procedures than in free tissue flap procedures (p=0.03). Free tissue flap procedures are potential reconstruction methods superior to jejunal flap methods.