Search

Background: Head and neck sarcomas are especially rare in Asia, leading to limited clinical evidence. This study aimed to investigate the incidence, clinical features, treatment status, and outcome of these sarcomas using data from the National Cancer Registry in Japan. Methods: All head and neck sarcomas diagnosed between 2016 and 2019 and recorded in the National Cancer Registry were analyzed. Data on sex, age, primary site, histological type, stage, treatment modality, and prognostic information were collected. Age-adjusted incidence and 3-year survival rates of patients with head and neck sarcomas were calculated. Results: Overall, 635 head and neck sarcoma patients were identified. Head and neck sarcoma occurred more frequently in men and patients in their 70 s. The age-adjusted annual incidence rate was 0.125 per 100,000 patients in the 2015 Japanese model or 0.089 per 100,000 patients in the world population model. The nasal cavity and paranasal sinuses were the most frequent primary sites, with rhabdomyosarcoma as the most common histologic type. Treatment typically involved chemotherapy and/or radiation therapy for rhabdomyosarcoma and Ewing's sarcoma, whereas surgical approaches for other types. Three-year survival rate of head and neck sarcoma patients was 64.8%. Conclusions: Head and neck sarcomas occurred rarely, but most frequently in the nasal cavity and paranasal sinuses in Japan. Poor outcomes were observed for sarcoma patients than for non-sarcoma head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Background: The correlation between L‐type amino acid transporter 1 (LAT1) expression and 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18F‐FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA positron emission tomography (PET). Methods: Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak), the minimum SUV (SUVmin), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated. Results: Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18F‐FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response. Conclusion: 18F‐FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies. [ABSTRACT FROM AUTHOR]

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center's experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the prognostic outcome for adolescent and young adult (AYA) generation patients with tongue squamous cell carcinoma (TSCC). Methods: Data were obtained from the Head and Neck Cancer Registry of Japan, and patients who were newly diagnosed with TSCC from 2011 to 2014 were extracted. We compared the clinical parameter and survival of the ≤ 39 years old (AYA) patient group with the 40–79 (non-AYA) group. Propensity score matching (PSM) was used for survival analyses. Results: Our cohort included 2221 patients with TSCC. AYA and non-AYA groups consisted of 258 and 1963 patients, respectively. The AYA group has a larger proportion of females than the non-AYA group (P < 0.001). Following PSM, both overall and disease-specific survival of the AYA group was significantly longer than those of the non-AYA group (P = 0.009 and P = 0.04, respectively). Conclusion: We demonstrated the survival superiority of AYA patients with TSCC compared to older adult patients. Therefore, our study results may reduce this anxiety by providing patients with appropriate information of prognosis for AYA patients with TSCC. [ABSTRACT FROM AUTHOR]

Background: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. Methods: We conducted a retrospective nationwide observational study on patients with T3–T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. Results: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%–19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. Conclusion: Omission of END during laryngectomy for T3–T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time. [ABSTRACT FROM AUTHOR]

The aim of this paper is to describe a safe and effective surgical technique for neck dissection under local anesthesia. An increasing number of patients cannot undergo general anesthesia due to systemic complication arising from old age. Moreover, the long‐term survival of patients with recurrent or metastatic cancer due to advances in chemotherapy has increased the necessity of neck dissection under local anesthesia. Appropriate pain control and selection of medical devices are important factors for success of the surgery under local anesthesia. In addition to the usual subcutaneous infiltration anesthesia for pain control, nerve blocks for each cervical nerve encountered during surgery are extremely effective. Since muscle relaxants are not available, sharp devices such as knife or scissors, instead of electric scalpel, should be used to prevent unexpected muscle contractions caused by electric current. This video presents well‐proven techniques and technical tips for superselective neck dissection under local anesthesia. This article supplements the Operative Techniques video presentation, which can be viewed online on Head & Neck's home page at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0347 [ABSTRACT FROM AUTHOR]

Abstract: The Japan Society for Head and Neck Surgery (JSHNS) started a board certification system for head and neck surgeons in 2010. To become certified, the following qualification and experiences are required: (1) board certification as otorhinolaryngologist, (2) 2 years of clinical experience in a board-certified training facility, (3) clinical care of 100 patients with head and neck cancer under the supervision of board-certified faculty and (4) surgical experience in 50 major head and neck surgical procedures, including 20 neck dissections, under the supervision of board-certified faculty. The following scientific activities are also required during the preceding 5 years: (1) two clinical papers on head and neck cancers presented at major scientific meetings, (2) one clinical paper on head and neck cancer published in a major journal, (3) attendance at two annual meetings of JSHNS and (4) enrolment in three educational programs approved by JSHNS. The qualifying examination consists of multiple choice tests and oral examinations. A total of 151 head and neck surgeons were certified in 2010 followed by 43 in 2011 and 34 in 2012, while the membership of JSHNS dramatically increased from 1201 in 2007 to 1748 in 2013. Although the board certification system for head and neck surgeons was started only recently, it has encouraged many residents and fellows as well as established head and neck surgeons. We believe that this system will contribute to further advancement in the clinical practice for head and neck cancers in Japan. [Copyright &y& Elsevier]

Copy number increase ( CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization ( FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade ( P = 0.047) and vascular invasion ( P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 ( P = 0.0005 log-rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [ HR]: 7.46; 95% confidence interval [ CI]: 1.98-28.06) and CNI of ACTN4 ( HR: 3.23; 95% CI: 1.08-9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Reconstructive surgery in which a free flap is used following extended resection for head and neck cancer has been popular for more than a quarter of a century. However, postoperative total flap necrosis has not been completely resolved, and few studies have analyzed the specific risk factors for this complication. Methods: Over a three-year period from 2005 to 2007, 388 flaps were used for reconstructive surgery on 384 patients at Department of Head and Neck of the Cancer Institute Hospital of Japanese Foundation for Cancer Research, and the results for 22 flaps with thrombosis were analyzed. Results: The only statistically significant risk factor for free flap thrombosis was the history of radical concurrent chemoradiotherapy. Conclusions: It will be necessary to keep this observation in mind when performing salvage surgery following chemoradiotherapy, which is expected to be performed more often in the future. [Copyright &y& Elsevier]

Abstract: Objective: There have been few reports addressing methods of dealing with free flap thrombosis after reconstructive surgery for head and neck cancer. The present study, through a detailed analysis of the subsequent course of patients who developed postoperative flap thrombosis, aims to clarify possible methods of salvage surgery in the event of vascular occlusion despite rigorous postoperative follow-up. Methods: We analyzed 59 cases of postoperative thrombosis in 1031 patients who underwent free flap transfer and considered the most appropriate salvage surgery in the event of total flap necrosis. Results: The flap salvage rate through vascular reanastomosis was highest for radial forearm flaps, with salvage of jejunal flaps being problematic if postoperative thrombosis occurred. For cases of postoperative thrombosis among patients who underwent reconstruction using a jejunal flap, the period of hospitalization was significantly extended for those patients in whom a second jejunal flap grafting was impossible. For cases of postoperative thrombosis among patients who underwent reconstruction using a radial forearm flap (FA), rectus abdominis flap (RA), or anterior lateral thigh flap (ALT), no significant difference was observed between those undergoing re-grafting with a free flap and those with a pedicled flap. Conclusion: We concluded that, among patients who undergo reconstruction using a jejunal flap, thrombosis should be discovered at an early stage to enable another jejunal flap re-grafting. For patients who undergo reconstruction using a FA, RA, or ALT, if thrombosis can be discovered at an early stage, there is a possibility of salvaging the flap by means of vascular reanastomosis. If it should prove impossible to salvage the flap, however, primary suture of the defect or reconstruction with a pedicled flap may also be considered. [Copyright &y& Elsevier]

Photoimmunotherapy for head and neck cancer (HNC-PIT) is a newly developed locoregional treatment targeting the epidermal growth factor. This treatment consists in administering cetuximab sarotalocan sodium that conjugates cetuximab with the dye IRdye700DX, which is activated by near-infrared ray illumination at 690 nm. HNC-PIT has been conditionally approved in Japan in September 2020 for the treatment of unresectable locally advanced or unresectable locoregionally recurrent HNC. However, its outcomes on the local recurrence of the nasopharyngeal squamous cell carcinoma (NPSCC) remain undetermined. In this report, we assessed the effects of HNC-PIT assisted by transnasal endoscopy on the local recurrence of NPSCC. A 77-year-old male presented with a local recurrence of NPSCC. The initial diagnosis revealed a squamous cell carcinoma, T2N2M0 stage III, positive for Epstein-Barr virus-encoded small RNA by in situ hybridization, which was treated with concurrent chemoradiotherapy (CRT). However, local recurrence was detected 14 months after CRT. We performed HNC-PIT under transnasal endoscopy. Seven months have passed since the HNC-PIT treatment, and the patient is alive without delayed adverse events and evidence of recurrence. Local recurrence of NPSCC, which is difficult to treat with minimally invasive surgery, is considered a potential candidate for HNC-PIT. [ABSTRACT FROM AUTHOR]

• Secondary analysis related to hypothyroidism (HT) in JCOG1008. • This is a HT report in a prospective study of postoperative chemoradiotherapy for head and neck cancer (HNC) patient. • In total, 16.7 % patients developed HT within 2 years after radiotherapy. • Weekly cisplatin using intensity-modulated radiotherapy was a HT factor. • V 60Gy potentially associated with the development of HT by intensity modulated radiation therapy. Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. In 2012–2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3–9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632–36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001–0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999–1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials. [ABSTRACT FROM AUTHOR]

Objective: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC).Methods: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0.Results: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC.Conclusion: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III). [ABSTRACT FROM AUTHOR]

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).Materials and Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future. [ABSTRACT FROM AUTHOR]

• Accelerator-BNCT produced tumor response in 71% of head and neck patients. • BNCT showed no serious adverse events such as grade 4 or 5, except hyperamylasemia. • The results support a pivotal role of accelerator BNCT in cancer treatment. Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck. [ABSTRACT FROM AUTHOR]

Background and purpose Borono-2- 18 F-fluoro-phenylalanine ( 18 F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while 18 F-fluorodeoxyglucose ( 18 F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between 18 F-BPA and 18 F-FDG uptakes using a deformable image registration-based technique. Material and methods Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body 18 F-BPA PET/computed tomography (CT) and 18 F-FDG PET/CT within a 2-week period. For each patient, 18 F-BPA PET/CT and 18 F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. Results Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between 18 F-BPA and 18 F-FDG showed a significant, positive correlation in the tumor volume. Conclusions Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between 18 F-BPA and 18 F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high 18 F-FDG uptake may predict high accumulation of 18 F-BPA. [ABSTRACT FROM AUTHOR]