Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/µL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/µL), with an average treatment effect of 98/µL (95% confidence interval [CI], 2-270/µL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/µL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/µL), with an average treatment effect (ATE) of 79/µL (95% CI, 19-171/µL); these EDEV levels remained elevated until day 5. CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas.

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti-CD44v10 mAb, C44Mab-18 (IgM, kappa), to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with the previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3-10-overexpressed CHO-K1 (CHO/CD44v3-10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody-dependent cellular cytotoxicity (ADCC) against CHO/CD44v3-10. In contrast, C44Mab-46-mG2a showed a superior complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CHO/CD44v3-10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.

Management of elderly patients with head and neck cancer.

There are no established guidelines for managing older patients with head and neck cancer. Most clinical trials that define current standard therapy included few elderly patients. On the other hand, there is great variability in patients' comorbidities, physical functions, cognitive function, familial and financial background and values. The key point appears to be appropriate geriatric assessment, clarifying the patients' outcomes and a multidisciplinary team approach, including the treatment decision-making policy. Although these processes should be scientific in nature, the evidence for the treatment of elderly head and neck patients is very limited. This review summarizes the evidence available regarding the management of geriatric assessment, each treatment modality and the multidisciplinary team approach for older patients with head and neck cancers.

The geriatric-8 screening tool for predicting complications in older adults after surgery for locally advanced head and neck cancer with free flap reconstruction.

PURPOSE: Radical surgery with free flap reconstruction for locally advanced head and neck cancer (HNC) is quite challenging for older adults. This retrospective study aimed to elucidate the usefulness of the geriatric-8 (G8) screening tool for predicting postoperative complications in older adults with HNC. METHODS: A retrospective review of 37 older adults with HNC who underwent radical surgery with free flap reconstruction and were assessed by the G8 screening tool was performed. Postoperative complications during hospitalization were classified according to the Clavien-Dindo classification, and possible contributing factors, including the G8 score, for major and minor complications were subjected to univariate and multivariate analyses. RESULTS: The appropriate G8 cut-off value for both major and minor complications was 12 (area under the curve 0.56 and 0.55, respectively). Multivariate logistic regression analysis showed that both smoking and lower G8 score (≤ 12) were independently associated with the severity of complications (p = 0.043, p = 0.034, respectively). CONCLUSIONS: The G8 was a possible predictor of major and minor complications in older adults with HNC who underwent radical surgery with free flap reconstruction.

Simultaneous evaluation of symptoms, swallowing functions, and patient-reported swallowing difficulties and their correlations with ingestion status during definitive chemoradiotherapy for oropharyngeal and hypopharyngeal cancer.

PURPOSE: To clarify the correlations among symptoms, swallowing functions, and ingestion status and to validate a method of swallowing evaluation during chemoradiotherapy (CRT) for head and neck cancer. METHODS: Oropharyngeal and hypopharyngeal cancer patients who were to receive definitive CRT as initial treatment were included in this prospective, single-center, observational study. The Functional Oral Intake Scale (FOIS) for ingestion status and grades of symptoms (dryness, dysgeusia, mucositis, and the analgesic ladder); the Yale Pharyngeal Residue Severity Rating Scale on fiberoptic endoscopic evaluation of swallowing (FEES) and the Penetration-Aspiration Scale (PAS) on videofluoroscopic (VF) evaluation for swallowing functions; and the 10-item Eating Assessment Tool (EAT-10) questionnaire were assessed at 5 time points unless the participant refused. The FEES and VF evaluation findings at each point were also compared. RESULTS: There were 38 participants. Dysgeusia, mucositis, and pain grade, as well as the FOIS score, were the worst at 70 Gy and then improved after treatment. The improvements of pharyngeal residue and the PAS after treatment were limited. The EAT-10 and the pain ladder were highly correlated with the FOIS changes at many time points. The VF evaluation rate dropped after 40 Gy, whereas the FEES rate remained high. There were good correlations between pharyngeal residue and the PAS at 0 Gy, 70 Gy, and 3 months. CONCLUSION: The EAT-10 and pain reflected the FOIS score changes well, while two swallowing evaluations did not. To avoid aspiration, VF evaluation may not be necessary during CRT because of high correlations with pharyngeal residue on FEES.

Simple laryngeal suspension procedure by suturing the digastric muscle to the periosteum of the mandible in neck dissection for tongue cancer.

PURPOSE: In this article, a simple, new laryngeal suspension procedure is described. The effect of hyoid bone suspension by suturing the digastric muscle to the periosteum of the mandible is analyzed. MATERIALS AND METHODS: To elucidate the effect of hyoid bone suspension, CT scans of 26 patients who underwent ipsilateral neck dissection with primary resection of tongue cancer were retrospectively reviewed, and the distance between the hyoid bone and the mandible was measured on the operated and unoperated sides of the neck. A total of 14 patients who underwent suturing of the digastric muscle to the mandible (digastric muscle-sutured group) and the 12 patients who did not (control group) were compared. RESULTS: In the digastric muscle-sutured group, the average distance between the hyoid bone and the mandible was significantly smaller on the operated side (17.8 ±â€¯0.57 mm) than on the unoperated side (19.8 ±â€¯0.93 mm; p < 0.05). In the control group, there was no significant difference between the operated side (21.0 ±â€¯1.42 mm) and the unoperated side (19.7 ±â€¯1.39 mm). The difference in the distance between the operated and unoperated sides was significantly larger in the digastric muscle-sutured group (1.97 ±â€¯0.79 mm) than in the control group (-1.32 ±â€¯0.61; p < 0.05). CONCLUSIONS: It was shown for the first time that suturing of the digastric muscle to the periosteum of the mandible in neck dissection with primary resection of tongue cancer resulted in hyoid bone suspension. This simple procedure can be useful for laryngeal suspension.

Poor oral intake causes enteral nutrition dependency after concomitant chemoradiotherapy for pharyngeal cancers.

PURPOSE: To identify precipitating factors responsible for enteral nutrition (EN) dependency after concomitant chemoradiotherapy (CCRT) of head and neck cancers and to examine their statistical correlations. METHODS: Factors related to feeding condition, nutritional status, disease, and treatment of 26 oropharyngeal and hypopharyngeal cancer patients who received definitive CCRT were retrospectively investigated by examining their medical records. The days of no oral intake (NOI) during hospitalization and the months using enteral nutrition after CCRT were counted as representing the feeding condition, and the changes in body weight (BW) were examined as reflecting nutritional status. The factors related to EN dependency after CCRT were analyzed. RESULTS: Long duration of total NOI (≥ 30 days) and maximum NOI ≥ 14 days were significant predictors of EN dependency. Decreased BW (≥ 7.5 kg) was the next predictor identified, but it was not significant. Multivariate analysis showed that the total duration of NOI was more correlated with EN dependency than changes in BW. CONCLUSIONS: A long duration of NOI was more strongly related to EN dependency than nutritional factors.

Clinical utility of dynamic-enhanced MRI in salivary gland tumors: retrospective study and literature review.

PURPOSE: To improve the diagnoses of the salivary gland tumors, a dynamic-enhanced MRI (dMRI) was investigated. METHODS: We conducted a retrospective chart review of 93 cases of salivary gland tumors. The histological diagnoses were obtained from all patients using a surgical specimen and/or an open biopsy specimen. The dMRI as well as fine-needle aspiration cytology (FNAC) and intraoperative frozen section (IFS) were analyzed. This study focused on the time-intensity curve (TIC) after injection, peak time (Tpeak), washout ratio (WR) as well as the gradient of enhancement and washout profile. RESULTS: The histological diagnoses included pleomorphic adenoma (PMA) in 53 cases, the Warthin tumors (WT) in 14 cases and malignant tumors (MT) in 26 cases. Incorrect diagnosis rate of FNAC and IFS were 5.2 and 8.3%, respectively. The TIC revealed differences among the three types of tumors. Tpeak as well as WR also revealed significant differences (p < 0.001). Tpeak were lower in order of WT, MT, PMA, respectively. WR of TICs at 30, 45 and 105 s after Tpeak were higher in order of WT, MT, PMA, respectively (p < 0.001). The gradient of increment and washout in the TIC curve was also an important parameter to distinguish the three types of tumors. In MT, the rapid enhancement pattern was found in high or intermediate histological grade tumors, whereas the slow enhancement pattern was exhibited in low grade tumors. CONCLUSIONS: Our findings indicate that using Tpeak and WR, it is possible to distinguish between WT, PMA and MT. Additionally, a rapid enhancement pattern may be a potential marker for these tumors.

Treatment of elderly patients with head and neck cancer in an aging society: Focus on geriatric assessment and surgical treatment.

Previous studies of the treatment of elderly head and neck cancer (HNC) patients were very limited and sometimes controversial. Although conclusions differ across various reports, it is often concluded that advanced chronological age does not directly affect prognosis, but that comorbidities and declines in physical and cognitive functions promote the occurrence of adverse events, especially with surgical treatment. Geriatric assessment (GA) and its screening tools are keys to help us understand overall health status and problems, predict life expectancy and treatment tolerance, and to influence treatment choices and interventions to improve treatment compliance. In addition, personal beliefs and values play a large role in determining policies for HNC treatment for elderly patients, and a multidisciplinary approach is important to support this. In this review, past research on HNC in older adults is presented, and the current evidence is explained, focusing on the management of elderly HNC patients, with an emphasis on the existing reports on each treatment stage and modality, especially the surgical procedures.

Breathing-Swallowing discoordination after definitive chemoradiotherapy for head and neck cancers is associated with aspiration pneumonia.

PURPOSE: Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing-swallowing coordination is an important factor in evaluating the risk of aspiration pneumonia. To investigate breathing-swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. METHODS: Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. RESULTS: Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing-swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. CONCLUSION: The results of this preliminary study indicate that breathing-swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks.

Multiple Buttresses Reconstruction of Maxilla with Fibular Flap Using Computer-aided Design/Computer-aided Manufacturing after Maxillectomy.

Background: The maxilla comprises horizontal and vertical buttresses, each with specific functions, supporting various organs, such as the eyes, nose, and oral cavity. Notably, they combine to form a three-dimensional structure, which enables the buttresses to provide their inherent support strength. However, reconstructing the maxilla after maxillectomy by assembling new buttresses is challenging. We successfully reconstructed all the buttresses crucial for facial appearance and dental rehabilitation using a vascularized fibular flap. Methods: Four patients underwent maxillary buttress reconstruction with a fibular flap after total or subtotal maxillectomy. We used computer-aided design/computer-aided manufacturing digital technology to osteotomize the fibula into multiple segments and assemble them to reconstruct the maxillary buttresses. Each buttress was assembled based on a preoperative simulation. Results: All patients underwent immediate one-stage maxillary reconstruction. They had good maxillary buttress alignment and acquired good facial appearance, eye position, nasal airway, and prosthetically suitable maxillary alveolus ridge. Conclusions: The combination of computer-aided design/computer-aided manufacturing digital technology and surgical techniques has enabled novel maxillary reconstruction, providing great hope to patients experiencing facial disfigurement and loss of function after maxillectomy.

Clinical characteristics and outcomes of persistent bacteremia in patients with head and neck cancer in a tertiary care hospital.

Introduction: Compared to other cancers, research on bloodstream infection in head and neck cancer is scarce, lacking comparative studies on persistent versus transient bacteremia outcomes. Methods: This retrospective survey examined patients with head and neck cancer undergoing blood culture at our center from June 2009 to May 2023. Blood culture-positive cases suspected of infection were divided into persistent bacteremia and transient bacteremia groups. We investigated their clinical, epidemiological, and microbiological features, including risk factors for persistent bacteremia and mortality. The primary outcome was 90-day mortality. Results: In this 97-patient cohort, 14 (14%) cases were assigned to the persistent bacteremia group. Catheter-related bloodstream infections were the leading cause of infection in both groups, consistently contributing to a high proportion of overall bloodstream infections. The mortality rate was generally higher in the persistent bacteremia group than in the transient bacteremia group (odds ratio [OR], 2.6; 95% confidence interval [CI], 0.6-11.1), particularly in the non-clearance subgroup (OR, 9; 95% CI, 0.5-155.2). Pyogenic spondylitis was a key risk factor for persistent bacteremia, while hypoalbuminemia increased mortality. Conclusion: In patients with bacteremia and head and neck cancer, persistent bacteremia was associated with higher mortality than was transient bacteremia. Adittionally, bacteremia clearance in persistent bacteremia is thus crucial for prognostic improvement.

Antitumor activities of anti­CD44 monoclonal antibodies in mouse xenograft models of esophageal cancer.

CD44 is a type I transmembrane glycoprotein associated with poor prognosis in various solid tumors. Since CD44 plays a critical role in tumor development by regulating cell adhesion, survival, proliferation and stemness, it has been considered a target for tumor therapy. Anti­CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody­drug conjugates and chimeric antigen receptor­T cell therapy. Anti-pan­CD44 mAbs, C44Mab­5 and C44Mab­46, which recognize both CD44 standard (CD44s) and variant isoforms were previously developed. The present study generated a mouse IgG2a version of the anti­pan­CD44 mAbs (5­mG2a and C44Mab­46­mG2a) to evaluate the antitumor activities against CD44­positive cells. Both 5­mG2a and C44Mab­46­mG2a recognized CD44s­overexpressed CHO­K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5­mG2a and C44Mab­46­mG2a could activate effector cells in the presence of CHO/CD44s cells and exhibited complement-dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5­mG2a and C44Mab­46­mG2a significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control mouse IgG2a. These results indicate that 5­mG2a and C44Mab­46­mG2a could exert antitumor activities against CD44­positive cancers and be a promising therapeutic regimen for tumors.

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.

Risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer receiving chemoradiotherapy: A re-analysis of a phase II/III JCOG1008 trial.

OBJECTIVES: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008. MATERIALS AND METHODS: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m2 (weekly arm) or 3-weekly cisplatin at 100 mg/m2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration. RESULTS: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %. CONCLUSIONS: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: 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.

Trismus after partial maxillectomy and radiotherapy: Free flap reconstruction versus prosthetic obturation.

OBJECTIVE: Partial maxillectomy and postoperative radiotherapy are both risk factors associated with trismus. This retrospective study aimed to evaluate the incidence and severity of trismus in patients following partial maxillectomy with or without postoperative radiotherapy and to compare free flap reconstruction and prosthetic obturation. METHODS: A retrospective review of 40 oral cancer patients who underwent partial maxillectomy with or without postoperative radiotherapy was performed. Maximum interincisal distance recorded at least 6 months after surgery was classified according to a revised subjective-objective management-analytical (SOMA) scale and compared between the free flap reconstruction group (n = 12) and the prosthetic obturation group (n = 28). RESULTS: Trismus was observed in 16/40 (40%) patients, and severe trismus was observed in 4/40 (10%) patients. Although no significant difference in trismus grade was observed between the free flap reconstruction and prosthetic obturation groups, both severe trismus and radiation-induced osteonecrosis were only seen in the prosthetic obturation group with postoperative radiotherapy. CONCLUSION: Free flap reconstruction was preferable to prosthetic obturation to avoid severe trismus and radiation-induced osteonecrosis in patients who underwent both partial maxillectomy and postoperative radiotherapy.

Imaging findings of arrested pneumatisation and differentiation from other skull base lesions.

OBJECTIVES: Arrested pneumatisation (AP) is an anatomic variant of the sphenoid sinus. Since AP remains underrecognised, otolaryngologists and radiologists may mistake AP for a lesion and perform follow-up imaging studies. We investigated the imaging findings of CT, MRI, and F-18 fludeoxyglucose (FDG)-positron emission tomography (PET) for AP, and discussed the differences between AP and other skull base lesions. METHODS: We reviewed multidetector low CT imaging of 442 patients (285 men and 157 women; age range, 19-93 years; mean age, 67.8 years) who underwent FDG-PET/CT for head and neck tumours between January 2019 and December 2019. The imaging findings of AP were reviewed on CT, MRI, FDG-PET/CT, and compared with those of fibrous dysplasia, chordoma, chondrosarcoma, multiple myeloma, and bone invasion of nasopharyngeal carcinoma. RESULTS: AP was identified in 22 patients (14 men and 8 women; age range, 24-93 years; mean age, 67.0 years) based on criteria from previous reports. AP manifested with well-circumscribed sclerotic margins on CT, without evidence of expansion. AP showed high-signal intensity on T1-/T2 weighted MRI. FDG-PET revealed non-significant uptake [maximum standardised uptake value (SUVmax): 0.85 (range, 0.4-1.27)] in AP. Contrastingly, skull base lesions showed expansion, poorly circumscribed boundaries without osteosclerotic margins, and moderate-to-severe FDG uptake (SUVmax: 1.8-8.4). CONCLUSIONS: The characteristic imaging findings of AP, namely non-expansile on CT and non-uptake on FDG-PET, may aid in its differentiation from other skull base lesions.

Preservation of remnant esophagus during total pharyngolaryngectomy in a patient with previous subtotal esophagectomy: a case report.

BACKGROUND: With the improved survival rate of patients with esophageal cancer, secondary cancers, including pharyngolaryngeal cancer, have become a problem. Phanryngolaryngeal cancer surgery often requires esophagogastric anastomosis resection in patients with a previous history of subtotal esophagectomy. Owing to adhesions, especially surrounding the esophagogastric anastomosis, caused by the initial surgery, the second surgery might cause postoperative complications. CASE PRESENTATION: A 65-year-old man was diagnosed with early stage esophageal squamous cell carcinoma and underwent endoscopic mucosal dissection. However, the histopathological depth of the tumor was pT1b, and additional treatment was required. After administration of the neoadjuvant chemotherapy, he underwent thoracoscopic esophagectomy and retrosternum reconstruction via a gastric tube (pT1N3M0 stage III). Eight months after the first surgery, tumor recurrences were observed at the anastomosis and left cervical lymph node. Definitive chemoradiotherapy was performed for the recurrences, and complete response was achieved. Seven months after chemoradiotherapy, he was diagnosed with hypopharyngeal squamous cell carcinoma in the right piriform fossa (cT2N2bM0 stage IVA), and salvage surgery was chosen as treatment. The surgical findings revealed strong adhesion around the remnant esophagus, which was difficult to dissect from surrounding tissue and was associated with a risk of breaking of the anastomosis. However, indocyanine green fluorescence imaging findings indicated sufficient blood flow to preserve the remnant esophagus, including the anastomosis, even after the interruption of blood flow from the proximal side of the esophagus by total pharyngolaryngectomy. Finally, approximately 4 cm of the remnant esophagus was preserved, and the free jejunum reconstruction with cervical vascular anastomosis was performed. Moreover, the patient was discharged without complications on postoperative day 38. After 10 months of the second surgery, a metastatic lymph node was observed in the right neck. Immune checkpoint inhibitors and chemotherapy were administered, and the patient is alive and under treatment 1.5 years after the second surgery. CONCLUSIONS: Blood supply to the remnant cervical esophagus was thought to be from the gastric conduit over the anastomosis and surrounding capillaries. Thus, the preservation of the remnant esophagus can be considered in total pharyngolaryngectomy even after < 2 years of esophagectomy by blood flow evaluation using indocyanine green fluorescence.