Essential data variables for a minimum dataset for head and neck cancer trials and clinical research: HNCIG consensus recommendations and database.

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.

Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

BACKGROUND: Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. METHODS: A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. RESULTS: Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6 months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7 months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1 months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4 months, which was superior to the median OS of 6.0 months for patients who received the best supportive care (log-rank p = 0.10). CONCLUSION: This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

BACKGROUND/AIM: Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). RESULTS: Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. CONCLUSION: The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

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.

Squamous cell carcinoma of the eyelid.

Eyelid squamous cell carcinoma is a major type of rare eyelid cancer, together with basal cell carcinoma and sebaceous gland carcinoma. It is a painless disease that progresses slowly and is often detected by the appearance of nodules or plaques. Risk factors include exposure to ultraviolet light, fair skin, radiation and human papillomavirus infection. The standard treatment is surgical removal, and in cases of orbital invasion, orbital content removal is required. If sentinel node biopsy reveals a high risk of lymph node metastasis, adjuvant radiotherapy may be considered. Local chemotherapy, such as imiquimod and 5-fluorouracil, may be used for eyelid squamous cell carcinoma in situ. When surgery or radiotherapy is not recommended for distant metastases or locally advanced disease, drug therapy is often according to head and neck squamous cell carcinoma in Japan. The treatment often requires a multidisciplinary team to ensure the preservation of function and cosmetic appearance.

Changes in serum DAMPs and cytokines/chemokines during near-infrared photoimmunotherapy for patients with head and neck cancer.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) for head and neck cancer is a recently developed therapy. However, there is limited data on patients receiving NIR-PIT in real clinical settings. METHODS: Seven NIR-PIT sessions were administered to five patients with head and neck squamous cell carcinoma (HNSCC). Serum damage-associated molecular patterns (DAMPs) (HMGB1 and Hsp70 levels), and cytokine and chemokine production, were compared before and after NIR-PIT. RESULTS: The serum concentration of HMGB1 increased after NIR-PIT (p = 0.031, Wilcoxon test) in all patients except one who did not achieve a clinical response. Chemokines MIP-1α (CCL3) and MIP-1ß (CCL4) increased significantly 1-3 days after treatment (CCL3, p = 0.0036; CCL4, p = 0.0016, Wilcoxon test). A low pre-treatment neutrophil-to-lymphocyte ratio (NLR) was associated with a better response to therapy and survival. CONCLUSIONS: The release of DAMPs, and cytokine/chemokine production, were detected in the patients' peripheral blood. The baseline NLR may predict patient outcomes in response to NIR-PIT.

The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer.

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.

Expression of CD5 in salivary gland tumors: an ancillary marker for carcinoma showing thymus-like differentiation (CASTLE) of the major salivary gland.

Recently, cases of carcinoma showing thymus-like differentiation (CASTLE) occurring in major salivary glands have been identified. To assess the diagnostic value of CD5 immunohistochemistry in distinguishing salivary CASTLE from other types of salivary gland tumors, we evaluated CD5 expression in 109 salivary gland tumors, encompassing 23 different histological types, including salivary CASTLE. In addition, we reviewed 10 previously reported cases of salivary CASTLE. Most salivary CASTLE cases (10/11, 91%) showed strong CD5 expression. In contrast, 104 of 108 (96%) non-salivary CASTLE tumors were negative for CD5, while the remaining four tumors (3.7%), all of which were histologically Warthin tumors, showed focal positivity for CD5 with weak to moderate intensity. In conclusion, the findings in this study support the potential use of CD5 immunohistochemistry for distinguishing salivary CASTLE from other histological types of salivary gland tumors. Aberrant CD5 expression in this tumor may be linked to the tumor microenvironment.

Peptide Receptor Radionuclide Therapy for Recurrent Olfactory Neuroblastoma After Cranioplasty for Surgical Infection: A Case Report.

BACKGROUND: Peputide receptor radionuclide therapy with 177Lu for midgut neuroendocrine metastasis has been clinically approved as a safe treatment. Unresectable metastases of olfactory neuroblastoma have shorter survival due to insufficient effective systemic treatment. CASE REPORT: Herein, we report a patient treated with peputide receptor radionuclide therapy for unresectable recurrent olfactory neusroblastoma following a rare cranial metastasectomy infection. A 50-year-old female patient with olfactory neuroblastoma of Kadish C was initially treated by skull base surgery plus postoperative radiotherapy following chemotherapy. Recurrent disease with neck and intracranial metastases was treated by four salvage surgeries. Surgical site infection following intracranial metastasectomy was treated with debridement and delayed cranioplasty. Peputide receptor radionuclide therapy was performed for unresectable multiple metastases after cranioplasty. Successful therapy using four cycles of peputide receptor radionuclide had neither grade 3 nor grade 4 adverse events. The patient was followed at an outpatient clinic. CONCLUSION: Further case accrual of peputide receptor radionuclide therapy is required to develop a treatment for unresectable olfactory neuroblastoma.

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis.

Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

Association Between 18F-Fluorodeoxyglucose Uptake and Mutation Status of Epidermal Growth Factor Receptor in Sinonasal Tract Cancer.

BACKGROUND/AIM: The Warburg effect of cancer has been applied to detect various carcinomas though the 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography with computed tomography (PET/CT). 18F-FDG-PET/CT in lung cancer predicted the mutation status of epidermoid growth factor receptor (EGFR). This study aimed to investigate whether 18F-FDG uptake parameters were significantly related to EGFR mutation status in patients with sinonasal tract squamous cell carcinoma (STSCC). PATIENTS AND METHODS: Twenty-nine tumor specimens of primary STSCC from patients with definitive treatment were collected. RESULTS: The 18F-FDG uptake from primary tumors was not different between mutant- and wild-status of EGFR on either Mann-Whitney U-test or the receiver operating curve. A metabolic tumor volume of ≥25 with the minimum p-value from the log-rank test for STSCC-specific survival was associated with a significantly shorter STSCC-specific, disease-free, local recurrence-free survival on the univariate and multivariate analyses adjusted for the clinical stage, treatment, and EGFR status. CONCLUSION: 18F-FDG-PET/CT did not predict mutation of the EGFR status in STSCC.

Current topics and management of head and neck sarcomas.

Given the low incidence, variety of histological types, and heterogeneous biological features of head and neck sarcomas, there is limited high-quality evidence available to head and neck oncologists. For resectable sarcomas, surgical resection followed by radiotherapy is the principle of local treatment, and perioperative chemotherapy is considered for chemotherapy-sensitive sarcomas. They often originate in anatomical border areas such as the skull base and mediastinum, and they require a multidisciplinary treatment approach considering functional and cosmetic impairment. Moreover, head and neck sarcomas may exhibit different behaviour and characteristics than sarcomas of other areas. In recent years, the molecular biological features of sarcomas have been used for the pathological diagnosis and development of novel agents. This review describes the historical background and recent topics that head and neck oncologists should know about this rare tumour from the following five perspectives: (i) epidemiology and general characteristics of head and neck sarcomas; (ii) changes in histopathological diagnosis in the genomic era; (iii) current standard treatment by histological type and clinical questions specific to head and neck; (iv) new drugs for advanced and metastatic soft tissue sarcomas; and (v) proton and carbon ion radiotherapy for head and neck sarcomas.

A novel technique in transoral robotic surgery: A case report of rotating and switching technique.

BACKGROUND: Transoral robotic surgery (TORS) for tongue base lesions located above the operative field is predominantly an upward procedure, which makes surgery difficult. METHODS: To illustrate our technique for this procedure, we report the case of an 82-year-old male with a p16-negative oropharyngeal carcinoma of the tongue base who underwent TORS. The field of view was turned upside down, and the operation switched the typical left- and right-arm functions. The daVinci Xi was docked, the 0° endoscope was rotated 180°, and the first arm was switched to the right hand and the third arm to the left hand. RESULTS: Although the lesion extended from the tongue base to the soft palate and mobile tongue, the planned resection line was followed. CONCLUSIONS: This technique improves operability by allowing downward manipulation and preventing the left and right arms from crossing. Further validation of the technique's effectiveness and safety is needed.

Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.

Utilization of ultrasound in photoimmunotherapy for head and neck cancer: a case report.

BACKGROUND: Photoimmunotherapy (PIT) is a new cancer treatment based on a different mechanism from conventional treatments that combines the administration of a photoabsorber and laser illumination. PIT has two characteristics: a high selectivity of target cells and the possibility of effects beyond the illuminated area. It is thus a potentially effective treatment for a wide variety of cancers. CASE PRESENTATION: We herein report a patient with oropharyngeal squamous cell carcinoma with superficial cervical lymph node recurrence. Intraoperative ultrasound confirmed the localization of the lesion and major vessels near the tumor. We punctured the tumor with catheters of laser illumination under ultrasound guidance. Laser illumination was able to be performed safely without causing serious adverse events, and the effect on the illuminated site was fully exhibited. CONCLUSIONS: Ultrasound allows for the intraoperative monitoring of each localized area and the puncture status easily in real-time. Accurate utilization of ultrasound is extremely important in PIT.