Effects of Chemotherapy and Radiation Therapy on Early Laryngeal Cancers.

Background/Aim: Treatments for early laryngeal squamous cell carcinoma (SCC) include radiotherapy (RT), chemoradiotherapy (CRT), and larynx-preserving surgery. In this study, early laryngeal SCC was treated with RT in patients with stage I (T1N0) tumors and with CRT and docetaxel (DOC) in patients with stage II (T2N0) tumors and the treatment results and effectiveness of the chemotherapy were compared. Patients and Methods: A total of 78 patients with early-stage laryngeal SCC were enrolled in this study. The T1N0 patients received radiation for the primary lesions as outpatients at a total dose of 63-70 Gy. By contrast, the T2N0 patients were hospitalized and treated with CRT, receiving a total radiation dose of 66-70 Gy. Docetaxel (DOC, 10 mg/m2) was administered intravenously once a week for 6-8 consecutive weeks concurrently with radiotherapy. The adverse events and survival rates with local control rates were examined. Results: The number of non-glottic T2N0 patients was significantly higher than that of T1N0 patients. Although all patients completed their treatment schedule, significantly more grade 3 adverse events were observed in the T2N0 patients, in particular mucositis and dermatitis, than in T1N0 patients. The 5-year overall survival rate, disease specific survival rate, local control rate, and laryngeal preserve rate of the T1N0 and T2N0 patients were 86.1, 93.3, 88.6, and 94.3% and 85.9, 88.0, 93.1, and 93.1%, respectively. Conclusion: CRT with docetaxel showed the best therapeutic outcomes for the treatment of laryngeal SCC in patients with T2N0 tumours, with a higher local control rate, effective laryngeal preservation, and relatively few adverse events.

Particle Beam Therapy and Surgery as Radical Treatments for Parotid Malignancies-A Single-Center Preliminary Case Study.

Background/Objectives: Particle beam therapy (PBT) was approved in April 2018 for head and neck malignancies and has since been introduced as a radical therapy for parotid malignancies. However, its prevalence and effectiveness in relation to surgical treatment have not been investigated. Methods: In this study, we evaluated 36 patients with parotid malignancy who underwent surgery (n = 26) or PBT (n = 10) and then analyzed the annual changes in the number of patients, survival rates, and clinical factors affecting prognosis. Results: Of the ten patients who opted for PBT, two and eight patients underwent PBT before and after 2018, respectively. There was a significant difference between these two groups of patients (p = 0.04). Of the ten patients who underwent PBT, five patients were recurrent cases; meanwhile, all twenty-six patients who underwent surgery were receiving initial treatment. Only one patient in each group had local recurrence after the treatment. Conclusions: The use of PBT as a radical therapy for parotid malignancies has been increasing since 2018, and patients with recurrent tumors tended to choose PBT. The outcome of the patients who underwent PBT did not seem to be inferior compared with those of the patients who underwent surgery. The histopathological type was a crucial issue in the outcomes of patients who underwent radical therapy for parotid malignancies.

Ultrasonographic diagnosis of cervical lymph nodes.

Many patients visit outpatient clinics suffering from cervical lymphadenopathy. For those patients, ultrasonography is useful in differentiating inflammatory diseases and malignant tumors. On ultrasonographic images, normal lymph nodes are indicated as hypoechogenic masses with a well-defined border. The medullary portion near the lymph node hilum is hyperechogenic, so-called fatty hilum (FH). Color Doppler imaging reveals that blood flows from the lymph node hilum to FH. In lymph node metastasis, a metastatic focus grows within lymph nodes, which displaces and destroys the structure of normal lymph nodes. Ultrasonography can be used to detect FH, disappearance and unevenness of blood flow within lymph nodes, cyst formation, and so on. It is important to closely observe the inside of lymph nodes and make a diagnosis via ultrasonography, based on the criteria for diagnosing lymph node metastasis from head and neck squamous cell carcinoma. Additionally, it is also necessary to distinguish among inflammatory lymphadenopathy and malignant lymphoma.

Childhood fever and hearing loss associated with CAPOS syndrome.

CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is a rare genetic disorder caused by the heterozygous mutation, c.2452G > A, in the ATP1A3 gene. CAPOS syndrome involves a characteristic episode in which neuropathy develops after a fever in childhood, and here, we describe the case of a patient with CAPOS syndrome. The patient had repeated episodes of a fever around 74 months of age. Although he could speak at 23 months of age, he presented with hearing difficulty after the fever. Pure-tone audiometry revealed moderate-to-severe bilateral sensorineural hearing loss, and auditory brainstem response (ABR) showed poor response in the both ears. Auditory stead-state response (ASSR) produced relatively consistent results compared to pure-tone audiometry. A mutation in the ATP1A3 gene was detected through genetic testing. In CAPOS syndrome, a genetic mutation leads to desynchronization during neural firing. We believe that this desynchronization in neural firing is responsible for the lack of response in the ABR and the presence of a response in the ASSR. In this patient, we attribute the response detection in ASSR to its greater tolerance for errors in the timing of neural firing compared to ABR.

Influence of COVID-19 pandemic on otitis media with effusion in children: A multicenter, retrospective survey in northern Japan.

OBJECTIVE: The purpose of this study is to compare patient trends in otitis media with effusion (OME) symptoms and diagnoses before and after the COVID-19 pandemic in order to investigate the effects of the coronavirus disease of 2019 (COVID-19). METHODS: A retrospective, multi-center, observational study was carried out between January 2018 and December 2022 at hospitals in the Iwate Prefecture with full-time doctors. All patients were initially separated into two groups, one for the pre-COVID-19 era (from January 2018 to June 2020), and the other for the COVID-19 era (from July 2020 to December 2022). RESULTS: In the pre-COVID-19 era, 132 patients had tympanostomy tubes (TT) placed, while 64 patients had them placed in the COVID-19 era. Between the pre-COVID-19 and COVID-19 eras, there were no statistically significant differences in terms of age, sex, side, craniofacial deformity, or adenoidectomy. Children in elementary school showed a greater decline than those in preschool (42-11 patients in elementary school (74%) and 49 to 32 patients in preschool school (35%); p = 0.025). CONCLUSIONS: The percentage of TT placements for OME dropped to roughly half during the COVID-19 epidemic. This was particularly obvious in elementary school students.

Patulous Eustachian Tube and Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis (OMAAV).

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic necrotizing vasculitis that affects small to medium-sized vessels. We describe two cases of patulous Eustachian tube (PET) in patients with otitis media with ANCA-associated vasculitis (OMAAV). The two cases presented in this paper had previously been diagnosed with Eustachian tube (ET) stenosis, and both presented with bilateral aural fullness, with one also experiencing postnasal drip and hearing loss. Both patients experienced positive myeloperoxidase (MPO)-ANCA and negative proteinase 3 (PR3)-ANCA, and treatment for ANCA-associated vasculitis (AAV) resulted in a diagnosis of PET. The patients were treated with transnasal self-installation of physiological saline into the pharyngeal orifice of the ET. This paper highlights the importance of considering PET in the differential diagnosis of OMAAV patients presenting with aural fullness.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Increasing Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma and its Oncologic Outcomes in the Rural Region in Northern Japan.

BACKGROUND/AIM: Despite the global rise in the incidence of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) in recent years, its prevalence and oncological outcomes in patients living in rural areas of Northern Japan has not been explored and should be investigated. PATIENTS AND METHODS: A total of 105 patients with oropharyngeal squamous cell carcinoma who underwent HPV screening and received first-line treatment were included in this study. The annual changes in the number of patients, survival rates, and clinical factors affecting prognosis were examined. RESULTS: The HPV-positive rate in patients with OPC was low, with the lowest rate of 10.0% in 2013 and the highest rate of 46.7% in 2020. The number of HPV-negative cases remained almost unchanged, whereas the overall number of cases increased with the increasing number of HPV-positive cases. Additionally, HPV-positive cases exhibited a fairly good prognosis. CONCLUSION: The number of OPC cases increased not only in urban areas, but also in rural areas. HPV-positive cases had better outcomes than HPV-negative cases.

A case report of angiosarcoma originating from the tongue.

Key Clinical Message: Angiosarcoma is a rare malignant disease with an extremely poor prognosis, showing rapid progression of the local tumor and/or distant metastases. Although multidisciplinary approach including systemic chemotherapy and radiation therapy is ideal for this disease, surgical resection have a role in disease control and should be performed as soon as possible. Abstract: Angiosarcomas originating from the tongue are rare and have extremely malignant features, leading to a poor prognosis. Herein, we report the case of a patient with angiosarcoma arising from the tongue who was successfully treated surgically. A 71-year-old man was diagnosed with a mass on the right side of his tongue and visited the Department of Oral and Maxillofacial Surgery at our hospital. The patient was referred to our department for further examination and treatment after a biopsy of the right edge of the tongue. An irregularly raised tumor 50 mm in length was noted on the right lingual border. The preoperative diagnosis was a primary angiosarcoma of the tongue (clinical stage, T3N2bM0, Stage IV). As his tumor had been growing rapidly, he emergently underwent partial right-sided tongue resection and right neck dissection without reconstructive surgery. The histopathological diagnosis was pT3N0. Postoperatively, the patient showed no signs of recurrence or metastasis during the 1-year follow-up. As for angiosarcomas, surgical resection is the only curative treatment, and surgery should be performed as soon as possible after the final diagnosis.

Systemic cisplatin increases the number of patients showing positive off-frequency masking audiometry.

OBJECTIVE: The study aimed to evaluate the effect of systemic cisplatin administration on off-frequency masking audiometry. METHODS: Among 26 patients receiving systemic cisplatin, 48 ears were included in the analysis. All patients underwent pure-tone audiometry with ipsilateral narrow-band masking noise (off-frequency masking audiometry). In the off-frequency masking audiometry, 70 dBHL band-pass noise (center frequency 1000 Hz, 1/3 octave bandwidth) was administered to the tested ear. The acquired thresholds were compared to those of standard pure-tone audiometry, and threshold elevations greater than 10 dB were regarded as significant. The number of patients showing abnormal threshold elevation was compared between before and after the cisplatin administration. RESULTS: Before cisplatin administration, 91.7, 93.8, 97.9, and 93.8% of ears showed normal off-frequency masking audiometry outcomes at 125, 250, 6000, and 8000 Hz, respectively. After cisplatin administration, a higher number of patients showed abnormal off-frequency masking audiometry outcomes. This change was more prominent with increasing doses of cisplatin. After the cisplatin administration of 100∼200 mg/m2, the prevalence of patients with normal off-frequency masking audiometry outcomes was 77.3, 70.5, 90.9, and 88.6% at 125, 250, 6000, and 8000 Hz, respectively. At 250 Hz, the change was statistically significant (p = 0.01, chi-squared test).

Intralymphatic injection of chemotherapy drugs modulated with glucose improves their anticancer effect.

Lymph node metastasis (LNM) has a significant impact on cancer prognosis, emphasizing the need for effective treatment strategies. This study investigated the potential use of high osmotic pressure drug solutions with low viscosity administration using a lymphatic drug delivery system (LDDS) to improve LNM treatment outcomes. The hypothesis was that injection of epirubicin or nimustine at high osmotic pressure but without altered viscosity would enhance drug retention and accumulation in LNs, thereby improving the efficacy of treatment. Biofluorescence analysis revealed enhanced drug accumulation and retention in LNs after administration using LDDS compared to intravenous (i.v) injection. Histopathological results demonstrated minimal tissue damage in the LDDS groups. Pharmacokinetic analysis revealed an improved treatment response with higher drug accumulation and retention in LNs. The LDDS approach offers the potential for greatly reduced side effects of chemotherapy drugs, lower dosage requirements and crucially increased drug retention in LNs. The results highlight the promise of high osmotic pressure drug solutions with low viscosity administrated using the LDDS for enhancing the treatment efficacy of LN metastasis. Further research and clinical trials are warranted to validate these results and optimize the clinical translation of this novel treatment technique.

A case of complete remission of Hodgkin lymphoma confirmed histopathologically by neck dissection.

BACKGROUND: Hodgkin lymphoma (HL) is diagnosed definitively by biopsy, and treatment is based on stage. Owing to the nature of the disease, post-treatment efficacy is determined mainly by fluorodeoxyglucose-positron emission tomography/computed tomography, and the efficacy of treatment is not confirmed by histopathology. We report a case of tongue cancer after treatment for HL, in which a post-treatment lymph node with complete remission was histopathologically confirmed by neck dissection. CASE: The patient was a 74-year-old man who was referred to our hospital for cancer on the right side of his tongue. He had previously undergone chemotherapy for HL involving the right side of his neck and achieved complete remission. Because he had cT3N2cM0 tongue cancer, glossectomy and bilateral neck dissection were performed. Surprisingly, histopathological examination revealed that there was neither metastatic lymph nodes nor lymphoma cells in his right neck. Moreover, there was no lymphatic structure in his remnant lymph nodes. CONCLUSION: This was a rare case in which complete remission of HL was confirmed by histopathological analysis. The absence of lymph node structure and lymphatic flow led to contralateral neck lymph node metastases of tongue cancer.

Management of cholesterol granuloma due to eosinophilic otitis media using large ventilation tube.

A 46-year-old man who had been diagnosed with eosinophilic otitis media (EOM) and eosinophilic chronic rhinosinusitis was referred to our department. He suffered from bilateral earache, clogged ear sensation, and otorrhea associated with EOM. He had been treated with a myringotomy and a ventilation tube (VT) insertion. However, his symptoms did not improve, and the VT repeatedly fell out. We performed canal wall down mastoidectomy via a retro-auricular incision to remove the presumed cholesterol granuloma (CG) and a long-term VT insertion. The VT fell out repeatedly. Therefore, a large VT that Komune devised was inserted. Four months after reinsertion, there was no evidence of recurrent otorrhea or fallout of a large VT. A large VT insertion could be useful in the severe case of EOM with CG.

Drug formulation augments the therapeutic response of carboplatin administered through a lymphatic drug delivery system.

Treatment of metastatic lymph nodes (LNs) is challenging due to their unique architecture and biophysical traits. Systemic chemotherapy fails to impede tumor progression in LNs due to poor drug uptake and retention by LNs, resulting in fatal systemic metastasis. To effectively treat LN metastasis, achieving specific and prolonged retention of chemotherapy drugs in the tumor-draining LNs is essential. The lymphatic drug-delivery system (LDDS) is an ultrasound-guided drug-delivery methodology for administration of drugs to LNs that addresses these requirements. However, early-stage metastatic LNs have an additional set of drug transport barriers, such as elevated intranodal pressure and viscosity, that negatively impact drug diffusion. In the present study, using formulations of elevated osmotic pressure and viscosity relative to saline, we sought to favorably alter the LN's physical environment and study its impact on pharmacokinetics and consequently the therapeutic efficacy of carboplatin delivered using the LDDS. Our study confirmed the capability of a drug formulation with elevated osmotic pressure and viscosity to alter the architecture of LNs, as it caused notable expansion of the lymphatic sinus. Additionally, the study delineated an optimal range of osmotic pressure and viscosity, centered around 1897 kPa and 11.5 mPa·s, above and below which therapeutic efficacy was found to decline markedly. These findings suggest that formulation osmotic pressure and viscosity are parameters that require critical consideration as they can both hinder and promote tumorigenesis. The facile formulation reported here has wide-ranging applicability across cancer spectrums and is thus anticipated to be of great clinical benefit.

Treatment Outcomes and Prognostic Factors of Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and Fluorouracil in Advanced Head and Neck Cancer.

BACKGROUND/AIM: Although the efficacy of docetaxel, cisplatin, and 5-Fluorouracil (TPF) as induction chemotherapy has been confirmed, the therapeutic outcome and prognostic factors of concurrent chemoradiotherapy (CCRT) should be investigated. PATIENTS AND METHODS: Laboratory data of patients who underwent CCRT for advanced squamous cell carcinoma (SCC) of the head and neck were investigated to clarify the grade of side effects. Survival rates and prognostic scores were also calculated. Multivariate analysis was performed to examine the prognostic factors of the patients. RESULTS: Although there were significantly more advanced cases in the TPF group (n=72) than those in the cisplatin group (n=50), there were no significant differences in patient survival rates. In the TPF group, the lymphocyte count, albumin level, and C-reactive protein level of the patients before treatment were significantly correlated with patient outcomes. CONCLUSION: CCRT using the TPF regimen had remarkable treatment effects in advanced head and neck cancer.

First-line pembrolizumab ± chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048.

BACKGROUND: Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab-chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). METHODS: Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67). RESULTS: At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09-0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25-1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31-1.41]). Pembrolizumab-chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23-2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55-2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55-2.22]). Median PFS was similar for pembrolizumab and pembrolizumab-chemotherapy versus EXTREME in all subgroups. Grades 3-5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab-chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab-chemotherapy died because of treatment-related pneumonitis. CONCLUSION: These results support the use of first-line pembrolizumab and pembrolizumab-chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031.

Primary rhabdomyosarcoma of the ethmoid sinus with orbital extension and metastasis to the pancreatic body.

This case report highlights the need for clinicians to monitor patients with rhabdomyosarcoma for pancreatic metastasis to ensure that proper treatment is quickly provided, thereby improving outcomes.

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial.

PURPOSE: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.