Induction chemotherapy with paclitaxel, carboplatin, and cetuximab (PCE) followed by chemoradiotherapy for unresectable locoregional recurrence after curative surgery in patients with squamous cell carcinoma of the head and neck.

Background: The significance of induction chemotherapy (IC) in the treatment of squamous cell carcinoma of the head and neck (SCCHN) with unresectable locoregional recurrence after curative surgery has not been clarified. The aim of this study was to evaluate the efficacy of IC followed by chemoradiotherapy (CRT) in these patients. Methods: Among patients with unresectable locoregional recurrent SCCHN who had not undergone prior irradiation and were eligible for cisplatin, we conducted a retrospective analysis of patients who received CRT following IC with paclitaxel, carboplatin, or cetuximab (IC-PCE group) and those who received CRT without prior IC (CRT group) between June 2013 and August 2021. Result: Forty-two patients were included. The CRT group and IC-PCE group consisted of 15 and 27 patients, respectively. Primary site was the oral cavity (n=25), oropharynx (n=3), hypopharynx (n=13) and larynx (n=1). Objective response rate (ORR) with IC-PCE was 55.6%; 24 patients (88.9%) subsequently received CRT. ORR after completion of CRT was significantly better in the IC-PCE group (95.8% in the IC-PCE group vs. 66.7% in the CRT group, p=0.024). Progression-free survival (PFS) of the total population on median follow-up of 2.4 years (range: 0.8-7.3) tended to be better in the IC-PCE group (2-year PFS: 55.6% in the IC-PCE group vs. 33.3% in the CRT group, log-rank p=0.176), especially in oral cancer (2-year PFS: 37.5% in the IC-PCE group vs. 0% in the CRT group, log-rank p=0.015). Conclusion: Therapeutic strategies including IC-PCE in patients with unresectable locoregional recurrent SCCHN after curative surgery may contribute to improved prognosis, especially in oral cancer.

Efficacy of anti-PD-1 monotherapy for recurrent or metastatic olfactory neuroblastoma.

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear. Methods: We retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy. Results: Of the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity. Conclusion: ICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB.

Precise synthesis of copper selenide nanowires with tailored Cu vacancies through photo-induced reduction for thermoelectric applications.

Nanostructuring in α-Cu2Se while optimizing carrier concentration holds the promise of realizing further high thermoelectric performance at near room temperature. Nevertheless, controlling the amounts of Cu vacancies, which work as acceptors, in nanostructures is considerably more intricate than in bulk materials. Hence, controlling the amounts of Cu vacancies while maintaining the α-phase and nanostructure shape poses a formidable challenge. In this study, we synthesized Cu2+x Se nanowires (NWs) with various amounts of Cu vacancies at room temperature by the photoreduction method and investigated their thermoelectric properties. Cu2+x Se NWs exhibited a comparable thermoelectric power factor to that of the polycrystalline films fabricated at higher temperature. The achievement of the high power factor despite low-temperature fabrication is attributed to the precise synthesis of Cu2+x Se NWs with various amounts of Cu vacancies. We also investigated the reaction process of Cu2.00Se NWs in detail by observing the reaction intermediates. It was found that photoreduction occurred with Cu2+ ions adsorbed on Se NWs, leading to the reaction of Cu2+ ions and Se NWs without Cu deficiency. Namely, this photoreduction under the adsorbed conditions realized the control of Cu vacancies in Cu2+x Se NWs.

Staggered structural dynamic-mediated selective adsorption of H2O/D2O on flexible graphene oxide nanosheets.

Graphene oxide (GO) is the one of the most promising family of materials as atomically thin membranes for water-related molecular separation technologies due to its amphipathic nature and layered structure. Here, we show important aspects of GO on water adsorption from molecular dynamics (MD) simulations, in-situ X-ray diffraction (XRD) measurements, and ex-situ nuclear magnetic resonance (NMR) measurements. Although the MD simulations for GO and the reduced GO models revealed that the flexibility of the interlayer spacing could be attributed to the oxygen-functional groups of GO, the ultra-large GO model cannot well explain the observed swelling of GO from XRD experiments. Our MD simulations propose a realistic GO interlayer structure constructed by staggered stacking of flexible GO sheets, which can explain very well the swelling nature upon water adsorption. The transmission electron microscopic (TEM) observation also supports the non-regular staggered stacking structure of GO. Furthermore, we demonstrate the existence of the two distinct types of adsorbed water molecules in the staggered stacking: water bonded with hydrophilic functional groups and "free" mobile water. Finally, we show that the staggered stacking of GO plays a crucial role in H/D isotopic recognition in water adsorption, as well as the high mobility of water molecules.

Type III Kounis Syndrome Caused by Iodine Contrast Media After Improvement of Allergic Symptoms.

Kounis syndrome is an acute coronary syndrome (ACS) caused by an allergic reaction that almost always occurs immediately and simultaneously with allergic symptoms. We present a case of Kounis syndrome type III that developed after complete resolution of contrast-induced anaphylaxis in a 60-year-old man with a coronary stent placed in the proximal left anterior descending (LAD) artery branch for ischemic heart disease. Contrast-enhanced computed tomography revealed anaphylactic shock. Symptoms quickly improved with intramuscular adrenaline injection; however, chest pain appeared after approximately 30 min. ECG revealed ST-wave elevation in the precordial leads. Coronary angiography revealed acute stent thrombosis with total occlusion of the proximal LAD, and percutaneous coronary angioplasty was performed. We diagnosed Kounis syndrome based on the allergic symptoms and ACS. Because some cases of Kounis syndrome develop after anaphylactic symptoms have resolved, it is advisable to follow-up patients with allergic symptoms and pay attention to chest symptoms and ECG changes, especially when they have a history of noted or treated coronary artery disease.

GenIce-core: Efficient algorithm for generation of hydrogen-disordered ice structures.

Ice is different from ordinary crystals because it contains randomness, which means that statistical treatment based on ensemble averaging is essential. Ice structures are constrained by topological rules known as the ice rules, which give them unique anomalous properties. These properties become more apparent when the system size is large. For this reason, there is a need to produce a large number of sufficiently large crystals that are homogeneously random and satisfy the ice rules. We have developed an algorithm to quickly generate ice structures containing ions and defects. This algorithm is provided as an independent software module that can be incorporated into crystal structure generation software. By doing so, it becomes possible to simulate ice crystals on a previously impossible scale.

Near-Infrared Fluorescence Imaging Sensor with Laser Diffuser for Visualizing Photoimmunotherapy Effects under Endoscopy.

The drug efficacy evaluation of tumor-selective photosensitive substances was expected to be enabled by imaging the fluorescence intensity in the tumor area. However, fluorescence observation is difficult during treatments that are performed during gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port. This device was employed to demonstrate that a laser diffuser with an NIR fluorescence imaging sensor could be delivered through a 3.2 mm diameter port. In addition, fluorescence images of Cetuximab-IR700 were successfully observed in two mice, and the fluorescence intensity confirmed that the fluorescence decayed within 330 s. This device is expected to have practical application as a tool to identify the optimal irradiation dose for tumor-selective photosensitive substances under endoscopy.

Nanoarchitectonics Solution Plasma Polymerization of Amino-Rich Carbon Nanosorbents for Use in Enhanced Fluoride Removal.

Amino-functionalized carbon (NH2C) is an effective adsorbent in removing pollutants from contaminated water because of its high specific surface area and electrical charge. In the conventional preparation method, the introduction of amino groups onto the carbon surface is limited, resulting in low pollutant adsorption. Herein, we present simultaneous carbonization and amination to form NH2C via electrical discharge of nonequilibrium plasma, and the resultant material is applied as an effective adsorbent in fluoride removal. The simultaneous process introduces numerous amino groups into the carbon framework, enhancing the adsorption efficiency. The fluoride adsorption capacity is approximately 121.12 mg g-1, which is several times higher than those reported in previous studies. Furthermore, computational modeling is performed to yield deeper mechanistic insights into the molecular-level adsorption behavior. These data are useful in designing and synthesizing advanced materials for applications in water remediation.

Cage occupancies of CH4, CO2, and Xe hydrates: Mean field theory and grandcanonical Monte Carlo simulations.

We propose a statistical mechanical theory for the thermodynamic stability of clathrate hydrates, considering the influence of the guest-guest interaction on the occupancies of the cages. A mean field approximation is developed to examine the magnitude of the influence. Our new method works remarkably well, which is manifested by two sorts of grandcanonical Monte Carlo (GCMC) simulations. One is full GCMC, and the other is designed in the present study for clathrate hydrates, called lattice-GCMC, in which each guest can be adsorbed at one of the centers of the cage. In the latter simulation, only the guest-guest interaction is explicitly treated, incorporating the host-guest interaction into the free energy of the cage occupation without other guests. Critical phenomena for guest species, such as large density fluctuations, are observed when the temperature is low or the guest-guest interaction is strong.

Catalytic Activity of Nonaggregating Cu Nanoparticles Supported in Pores of Zeolite for Aerobic Oxidation of Benzyl Alcohol.

Cu nanoparticles (NPs) as catalysts have the good advantage of being more abundant than noble metal NPs. In this study, we synthesized nonaggregating Cu NPs supported in Y-type zeolite by the photoreduction method. In this method, Cu ions in pores of zeolite can be slowly reduced with a small amount of reductant at room temperature. The high-resolution transmission electron microscope, energy dispersive X-ray spectroscopy, X-ray diffraction patterns, and UV-Vis spectra supported that nonaggregating Cu NPs existed in the pores of zeolite. Catalytic activities of Cu NP-zeolite were investigated for the aerobic oxidation of benzyl alcohol. Our Cu NP-zeolite had a large turnover frequency of 17 h-1. The yield of benzaldehyde increased in proportion to the amount of Cu loading at ≤0.5 wt %, indicating that Cu NPs in pores of zeolite work as catalysts for selective aerobic oxidation of benzyl alcohol. The high catalytic activity was brought by nonaggregating Cu NPs in pores of zeolite. The catalytic reaction for other aromatic alcohols with electron-donating groups proceeded, whereas it did not proceed for the aromatic alcohols with electron-withdrawing groups or aliphatic alcohols, indicating that the interaction between zeolite and the benzene ring also contributed to the reaction. This study would be expected to contribute to the development of Cu NP catalysts.

Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck.

Background: Immune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects' prognosis. Methods: We retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy. Results: Of 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed. Conclusion: PE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN.

Weekly paclitaxel, carboplatin and cetuximab (PCE) combination followed by nivolumab for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

OBJECTIVES: Cetuximab-based chemotherapy is a standard 1st-line treatment for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, few studies have reported survival data for a treatment sequence consisting of a PCE regimen (paclitaxel + carboplatin + cetuximab) followed by an immune checkpoint inhibitor. MATERIALS AND METHODS: We retrospectively assessed 37 patients with R/M SCCHN from the oral cavity, oropharynx, hypopharynx, and larynx who received PCE as 1st-line treatment followed by nivolumab as 2nd-line at the National Cancer Center Hospital East between December 2016 and July 2021. For comparison, we also analyzed 14 patients who did not receive nivolumab after PCE. RESULTS: Of the 37 patients who received nivolumab, overall response rate (ORR) by PCE was 48.6%, and median time to response and median progression-free survival (PFS) were 2.1 months (range: 0.8-4.8) and 4.4 months, respectively. In the nivolumab phase, ORR was 10.8%. 23 patients received 3rd-line therapy. Median PFS2, PFS3, and overall survival (OS) were 6.8, 11.6, and 19.5 months, respectively. Subgroup analysis by PD-L1 expression showed no significant difference in OS. Analysis of the comparison group revealed a trend toward improved OS in those who received nivolumab compared to those who did not (HR 0.47, 95%CI [0.19-1.13], p = 0.084). CONCLUSION: PCE followed by nivolumab shows a favorable survival outcome, representing the potential for rapid tumor response with PCE and extension of OS by the addition of nivolumab regardless of combined positive score.

Efficiency and energy balance for substitution of CH4 in clathrate hydrates with CO2 under multiple-phase coexisting conditions.

Many experimental and theoretical studies on CH4-CO2 hydrates have been performed aiming at the extraction of CH4 as a relatively clean energy resource and concurrent sequestration of CO2. However, vague or insufficient characterization of the environmental conditions prevents us from a comprehensive understanding of even equilibrium properties of CH4-CO2 hydrates for this substitution. We propose possible reaction schemes for the substitution, paying special attention to the coexisting phases, the aqueous and/or the fluid, where CO2 is supplied from and CH4 is transferred to. We address the two schemes for the substitution operating in three-phase and two-phase coexistence. Advantages and efficiencies of extracting CH4 in the individual scheme are estimated from the chemical potentials of all the components in all the phases involved in the substitution on the basis of a statistical mechanical theory developed recently. It is found that although substitution is feasible in the three-phase coexistence, its working window in temperature-pressure space is much narrower compared to the two-phase coexistence condition. Despite that the substitution normally generates only a small amount of heat, a large endothermic substitution is suggested in the medium pressure range, caused by the vaporization of liquid CO2 due to mixing with a small amount of the released CH4. This study provides the first theoretical framework toward the practical use of hydrates replacing CH4 with CO2 and serves as a basis for quantitative planning.

Chemistry of zipping reactions in mesoporous carbon consisting of minimally stacked graphene layers.

The structural evolution of highly mesoporous templated carbons is examined from temperatures of 1173 to 2873 K to elucidate the optimal conditions for facilitating graphene-zipping reactions whilst minimizing graphene stacking processes. Mesoporous carbons comprising a few-layer graphene wall display excellent thermal stability up to 2073 K coupled with a nanoporous structure and three-dimensional framework. Nevertheless, advanced temperature-programmed desorption (TPD), X-ray diffraction, and Raman spectroscopy show graphene-zipping reactions occur at temperatures between 1173 and 1873 K. TPD analysis estimates zipping reactions lead to a 1100 fold increase in the average graphene-domain, affording the structure a superior chemical stability, electrochemical stability, and electrical conductivity, while increasing the bulk modulus of the framework. At above 2073 K, the carbon framework shows a loss of porosity due to the development of graphene-stacking structures. Thus, a temperature range between 1873 and 2073 K is preferable to balance the developed graphene domain size and high porosity. Utilizing a neutron pair distribution function and soft X-ray emission spectra, we prove that these highly mesoporous carbons already consist of a well-developed sp2-carbon network, and the property evolution is governed by the changes in the edge sites and stacked structures.

Combination chemotherapy with taxane and platinum in patients with salivary gland carcinoma: a retrospective study of docetaxel plus cisplatin and paclitaxel plus carboplatin.

Background: Despite advances in precision medicine, most patients with recurrent or metastatic salivary gland carcinoma still need conventional chemotherapies, such as the combination of taxane and platinum. However, evidence for these standardized regimens is limited. Methods: We retrospectively reviewed patients with salivary gland carcinoma treated with a taxane and platinum, which contained docetaxel at a dose of 60 mg/m2 plus cisplatin at a dose of 70 mg/m2 on day 1, or paclitaxel at a dose of 100 mg/m2 plus carboplatin at a dose of area under the plasma concentration-time curve = 2.5 on days 1 and 8 (both on 21-day cycles), between January 2000 and September 2021. Result: Forty patients with ten adenoid cystic carcinomas and thirty other pathologies were identified. Of these, 29 patients were treated with docetaxel plus cisplatin and 11 with paclitaxel plus carboplatin. For the total population, the objective response rate (ORR) and median progression-free survival (mPFS) were 37.5% and 5.4 months (95% confidence interval: 3.6-7.4 months), respectively. On subgroup analysis, docetaxel plus cisplatin provided favorable efficacy compared with paclitaxel plus carboplatin (ORR: 46.5% vs. 20.0%, mPFS: 7.2 vs. 2.8 months), and the findings were well retained in patients with adenoid cystic carcinoma (ORR: 60.0% vs. 0%, mPFS: 17.7 vs. 2.8 months). Grade 3/4 neutropenia was relatively frequent in the docetaxel plus cisplatin (59% vs.27%), although febrile neutropenia was uncommon (3%) in the cohort. No treatment-related death was seen in any case. Conclusion: The combination of taxane and platinum is generally effective and well-tolerated for recurrent or metastatic salivary gland carcinoma. In contrast, paclitaxel plus carboplatin appears unfavorable in terms of efficacy in certain patients, such as those with adenoid cystic carcinoma.

On the phase behaviors of CH4-CO2 binary clathrate hydrates: Two-phase and three-phase coexistences.

We develop a statistical mechanical theory on clathrate hydrates in order to explore the phase behaviors of clathrate hydrates containing two kinds of guest species and apply it to CH4-CO2 binary hydrates. The two boundaries separating water and hydrate and hydrate and guest fluid mixtures are estimated, which are extended to the lower temperature and the higher pressure region far distant from the three-phase coexisting conditions. The chemical potentials of individual guest components can be calculated from free energies of cage occupations, which are available from intermolecular interactions between host water and guest molecules. This allows us to derive all thermodynamic properties pertinent to the phase behaviors in the whole space of thermodynamic variables of temperature, pressure, and guest compositions. It is found that the phase boundaries of CH4-CO2 binary hydrates with water and with fluid mixtures locate between simple CH4 and CO2 hydrates, but the composition ratios of CH4 guests in hydrates are disproportional to those in fluid mixtures. Such differences arise from the affinities of each guest species to the large and small cages of CS-I hydrates and significantly affect occupation of each cage type, which results in a deviation of the guest composition in hydrates from that in fluid on the two-phase equilibrium conditions. The present method provides a basis for the evaluation of the efficiency of the guest CH4 replacement to CO2 at the thermodynamic limit.

Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment options for improved survival or quality of life. To date, however, few reports have addressed the efficacy of LT for sites of disease progression after immune checkpoint inhibitors, including other cancers. METHODS: We conducted a retrospective analysis of patients with R/M SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx and treated with nivolumab. We extracted patients undergoing salvage LT or palliative radiotherapy (RT) to the selected progressive lesion at any time after initiation of nivolumab. RESULTS: Twenty-four patients received LT. Salvage LT was performed in 9 (37.5%) patients, including surgery and definitive RT in 5 and 4 patients, respectively. Palliative RT was performed in 15 (62.5%) patients. LT was provided in 10 (41.7%) patients for oligoprogressive disease. Twelve (50.0%) patients received subsequent systemic therapy immediately after LT. Classification based on patient treatment divided the population into four subgroups with different prognoses (salvage LT followed by subsequent systemic therapy [n = 3], salvage LT alone [n = 6], palliative RT followed by subsequent systemic therapy [n = 9], and palliative RT alone [n = 6]). Median OS in this order was 24.5, 9.0, 7.3, and 2.4 months (p = 0.001). All patients in the salvage LT followed by subsequent systemic therapy group continued nivolumab. CONCLUSION: In R/M SCCHN patients who have received nivolumab, salvage LT for the selected progressive lesion with continuation of nivolumab potentially provides an excellent survival prognosis.

Edge-Site-Free and Topological-Defect-Rich Carbon Cathode for High-Performance Lithium-Oxygen Batteries.

The rational design of a stable and catalytic carbon cathode is crucial for the development of rechargeable lithium-oxygen (LiO2 ) batteries. An edge-site-free and topological-defect-rich graphene-based material is proposed as a pure carbon cathode that drastically improves LiO2 battery performance, even in the absence of extra catalysts and mediators. The proposed graphene-based material is synthesized using the advanced template technique coupled with high-temperature annealing at 1800 °C. The material possesses an edge-site-free framework and mesoporosity, which is crucial to achieve excellent electrochemical stability and an ultra-large capacity (>6700 mAh g-1 ). Moreover, both experimental and theoretical structural characterization demonstrates the presence of a significant number of topological defects, which are non-hexagonal carbon rings in the graphene framework. In situ isotopic electrochemical mass spectrometry and theoretical calculations reveal the unique catalysis of topological defects in the formation of amorphous Li2 O2 , which may be decomposed at low potential (∼ 3.6 V versus Li/Li+ ) and leads to improved cycle performance. Furthermore, a flexible electrode sheet that excludes organic binders exhibits an extremely long lifetime of up to 307 cycles (>1535 h), in the absence of solid or soluble catalysts. These findings may be used to design robust carbon cathodes for LiO2 batteries.

Chronic epidural hematoma with frontal skull-base destruction mimicking osteogenic tumor, associated with coagulopathy due to chronic hepatitis C.

Background: Intracranial epidural hematoma is generally evoked by acute coup-injury. Though rare, it has a chronic clinical course and can be a non-traumatic event. Case Description: The patient was A thirty-five-year-old man with a complaint of one-year history of hand tremor. He was suspected diagnosis of osteogenic tumor with differential diagnosis of epidural tumor, or abscess in the right frontal skull base bone, associated with chronic type C hepatitis because of his plain CT and MRI. Results: Results of examinations and surgery, the extradural mass was chronic epidural hematoma without skull fracture. We diagnosis he is the rare case of chronic epidural hematoma caused by coagulopathy due to chronic hepatitis C. Conclusion: We reported a rare case of chronic epidural hematoma caused by coagulopathy due to chronic hepatitis C. The repeated spontaneous hemorrhage in the epidural space formed the capsule and destruction of skull base bone, just mimicking skull base tumor.

Proton pump inhibitors and antibiotics adversely effect the efficacy of nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Several reports have shown that the use of proton pump inhibitors (PPIs) and antibiotics (Abx) can reduce the efficacy of immune checkpoint inhibitors in various cancers. To date, however, the association of immune checkpoint inhibitors with PPI and/or Abx in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) has not been reported. METHODS: We retrospectively reviewed patients with platinum-refractory R/M SCCHN treated with nivolumab from May 2017 and March 2020 in our institute. Primary sites included the oral cavity, oropharynx, hypopharynx and larynx. The relationship between prognostic parameters, such as overall survival (OS), progression-free survival (PFS), PFS2 and PFS3, and clinical factors, including PPI or Abx use, was examined, and the creation of prognostic classification was also attempted. RESULTS: Of 110 patients identified, 56 patients received PPI and 24 patients received Abx within 30 days before or after the initiation of nivolumab. With a median follow-up of 17.2 months (range: 13.8-25.0), median PFS, PFS2, PFS3 and OS were 3.2, 8.1, 14.0 and 17.2 months, respectively. In univariate analysis, the use of PPI and of Abx was significantly associated with poor prognosis in all parameters (PFS, PFS2, PFS3 and OS). Median OS (hazard ratio; 95%confidence interval, p-value) by these covariates were 13.6 versus 23.8 months (1.70; 1.01-2.87, p = 0.046) for PPI and 10.0 versus 20.1 months (1.85; 1.00-3.41, p = 0.048) for Abx, respectively. Furthermore, these factors showed mutually independent adverse associations on multivariate analysis. CONCLUSION: The use of PPI and Abx attenuated the efficacy of nivolumab in R/M SCCHN. Further prospective evaluation is warranted.