Clinical impact of a dose-escalation strategy for lenvatinib in differentiated thyroid cancer.

BACKGROUND:  Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated. METHODS: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose. RESULTS: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0-NA] vs. 3.9 months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess. CONCLUSION: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.

Effects of Thickening Agents on the Mucociliary Transport Function: Comparison by the Type of Thickening Agents and the Viscosity of Thickened Water.

Thickening agents effectively prevent liquid aspiration, but their impact on the ease of discharging aspirated liquids from the trachea remains unclear due to alterations in the physical properties of liquids. This study clarifies the effects of thickening agents, comprising various raw materials, on mucociliary transport function, focusing on the viscosities of thickened waters. The subjects were 23 healthy adults. Five types of saccharin solution were prepared: a solution without a thickening agent, a starch-based nectar-like solution, a starch-based honey-like solution, a xanthan-gum-based nectar-like solution, and a xanthan-gum-based honey-like solution. Using these five types of saccharin solutions randomly, each subject underwent five trials of the saccharine dye test to evaluate the mucociliary transport function of the respiratory tract. The saccharin time was defined as the time from the placement of the saccharin solution on the nasal vestibule of the subject to when the subject reported that they became aware of the sweetness. The saccharin transit times for all samples of thickened water were longer compared to those of water without a thickening agent (p < 0.01). A comparison between thickened water samples with different viscosities showed that the saccharin transit time was longer when thickened water samples with high viscosity were prepared using the same thickening agent (p < 0.01). This suggests that while thickening reduces aspiration, the use of thickening agents may increase the difficulty in discharging aspirated fluids from the trachea.

Isolation and characterization of blackish-brown BY2-melanin accumulated in cultured tobacco BY-2 cells.

The tobacco BY-2 cell line is one of the most utilized plant cell lines. After long-term culture, the cells turn brown to black, but the causal pigment is unknown. We successfully isolated a blackish-brown pigment from BY-2 cells cultured for 3 weeks. Morphological and spectroscopic analyses indicated that the pigment had similar features to a melanin-like substance reported previously. Furthermore, physicochemical analyses revealed that this pigment possessed most of the properties of melanin-like pigments. In addition, the high nitrogen content suggested that it differed from common plant melanins classified as allomelanins, suggesting a novel eumelanin-like pigment: "BY2-melanin". This is the first example showing that eumelanin-like pigments are produced in the cultures of plant cells for which the accumulation of melanin has not been reported. This tobacco BY-2 cell culture technique may represent a customizable and sustainable alternative to conventional melanin production platforms, with significant potential for industrial and pharmacological applications.

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.

Production of Agrocinopine A by Ipomoea batatas Agrocinopine Synthase in Transgenic Tobacco and Its Effect on the Rhizosphere Microbial Community.

Agrobacterium tumefaciens is a bacterial pathogen that causes crown gall disease on a wide range of eudicot plants by genetic transformation. Besides T-DNA integrated by natural transformation of plant vegetative tissues by pathogenic Agrobacterium spp., previous reports have indicated that T-DNA sequences originating from an ancestral Agrobacterium sp. are present in the genomes of all cultivated sweet potato (Ipomoea batatas) varieties analyzed. Expression of an Agrobacterium-derived agrocinopine synthase (ACS) gene was detected in leaf and root tissues of sweet potato, suggesting that the plant can produce agrocinopine, a sugar-phosphodiester opine considered to be utilized by some strains of Agrobacterium spp. in crown gall. To validate the product synthesized by Ipomoea batatas ACS (IbACS), we introduced IbACS into tobacco under a constitutive promoter. High-voltage paper electrophoresis followed by alkaline silver nitrate staining detected the production of an agrocinopine-like substance in IbACS1-expressing tobacco, and further mass spectrometry and nuclear magnetic resonance analyses of the product confirmed that IbACS can produce agrocinopine A from natural plant substrates. The partially purified compound was biologically active in an agrocinopine A bioassay. A 16S ribosomal RNA amplicon sequencing and meta-transcriptome analysis revealed that the rhizosphere microbial community of tobacco was affected by the expression of IbACS. A new species of Leifsonia (actinobacteria) was isolated as an enriched bacterium in the rhizosphere of IbACS1-expressing tobacco. This Leifsonia sp. can catabolize agrocinopine A produced in tobacco, indicating that the production of agrocinopine A attracts rhizosphere bacteria that can utilize this sugar-phosphodiester. These results suggest a potential role of IbACS conserved among sweet potato cultivars in manipulating their microbial community.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Biweekly administration of cetuximab in Japanese patients with recurrent or metastatic head and neck cancer.

BACKGROUND: Cetuximab (Cmab) plays an important role in the treatment for recurrent or metastatic head and neck cancer (R/M HNC). To date, however, no safety data on biweekly administration of cetuximab at a dose of 500 mg/m2 (biweekly Cmab) for Japanese HNC patients have been available. METHODS: We retrospectively reviewed the clinical records of five R/M HNC patients who received biweekly Cmab in our institute between January 2016 and September 2021 and compared the safety profile between two phases of weekly 250 mg/m2 and biweekly 500 mg/m2 Cmab in the identical patients. RESULTS: All patients initially received Cmab in combination with chemotherapy. Chemotherapy consisted of paclitaxel plus carboplatin in two patients, cisplatin + 5-FU in one patient, and paclitaxel in two patients. Three patients switched treatment schedule from weekly Cmab to biweekly Cmab, while two patients received biweekly Cmab after completion of chemotherapy. The main reason for switching to biweekly Cmab was an unacceptably long commuting time to the hospital. The median duration of Cmab was 217 days (49-321) during weekly Cmab with or without chemotherapy and 42 days (28-175) during biweekly Cmab. Median dose of biweekly Cmab was 4 (3-12). During biweekly Cmab, worsened (Grade ≥ 2) toxicities were observed in two patients: one with grade 2 dry skin and the second with grade 2 skin infection. None developed grade ≥ 3 adverse events or discontinued treatment due to Cmab-related adverse events. CONCLUSION: Biweekly Cmab was well tolerated and did not demonstrate severe toxicities related to Cmab for R/M HNC.

Relationship between daily swallowing frequency and pneumonia in patients with severe cerebral palsy.

BACKGROUND: Aspiration pneumonia is a major complication that occurs in patients with severe cerebral palsy and is associated with their survival prognosis, necessitating appropriate assessment and response. We focused on swallowing frequency as an index of daily swallowing function due to the difficulty in evaluating the risk of pneumonia. The swallowing motion protects the airway by safely directing the food, saliva, and secretions accumulated in the pharynx into the esophagus to prevent aspiration and entry into the trachea. Thus, swallowing frequency may be correlated with the incidence of pneumonia. In this study, we aimed to investigate the relationship between swallowing frequency and history of pneumonia in patients with severe cerebral palsy. METHODS: Fifty-seven patients with cerebral palsy were included in this study. Swallowing frequency was measured three times for each patient on separate days, and the reproducibility was examined by calculating the intraclass correlation coefficient. Further, the relationship between swallowing frequency and history of pneumonia was investigated using multivariate logistic regression analysis. RESULTS: While swallowing frequency differed between participants, it was constant within individuals (intraclass correlation coefficient: 0.941). Furthermore, the swallowing frequencies per hour were 12.2 ± 12.2 and 27.0 ± 20.4 in the patient groups with and without a history of pneumonia, respectively (P < 0.001). Swallowing frequency (odds ratio: 10.489, 95% confidence interval: 2.706-40.663, P = 0.001) was significantly associated with the incidence of pneumonia in the previous year. CONCLUSIONS: Swallowing frequency could be used as an index for assessing the risk of dysphagia and pneumonia in patients with severe cerebral palsy.

Expression of a fungal exo-ß-1,3-galactanase in Arabidopsis reveals a role of type II arabinogalactans in the regulation of cell shape.

Arabinogalactan-proteins (AGPs) are a family of plant extracellular proteoglycans implicated in many physiological events. AGP is decorated with type II arabinogalactans (AGs) consisting of a ß-1,3-galactan backbone and ß-1,6-galactan side chains, to which other sugars are attached. Based on the fact that a type II AG-specific inhibitor, ß-Yariv reagent, perturbs growth and development, it has been proposed that type II AGs participate in the regulation of cell shape and tissue organization. However, the mechanisms by which type II AGs participate have not yet been established. Here, we describe a novel system that causes specific degradation of type II AGs in Arabidopsis, by which a gene encoding a fungal exo-ß-1,3-galactanase that specifically hydrolyzes ß-1,3-galactan backbones of type II AGs is expressed under the control of a dexamethasone-inducible promoter. Dexamethasone treatment increased the galactanase activity, leading to a decrease in Yariv reagent-reactive AGPs in transgenic Arabidopsis. We detected the typical oligosaccharides released from type II AGs by Il3GAL in the soluble fraction, demonstrating that Il3GAL acted on type II AG in the transgenic plants. Additionally, this resulted in severe tissue disorganization in the hypocotyl and cotyledons, suggesting that the degradation of type II AGs affected the regulation of cell shape.

Effect of aspiration on the lungs in children: a comparison using chest computed tomography findings.

BACKGROUND: Detecting and addressing aspiration early in children with dysphagia, such as those with cerebral palsy, is important for preventing aspiration pneumonia. The current gold standards for assessing aspiration are swallowing function tests, such as fiberoptic endoscopic evaluation of swallowing (FEES) and videofluorographic swallowing study; however, the relationship between aspiration of secretion vs aspiration of foodstuff and pulmonary injury is unclear. To clarify this relationship, we examined the correlations between pneumonia findings from chest computed tomography (CT) and the presence or absence of aspiration detected by FEES. METHODS: Eighty-five children (11 years 2 months ±7 years 2 months) underwent FEES and chest CT. Based on the FEES findings, the participants were divided into groups: with and without food aspiration, and with and without saliva aspiration. Correlations between chest CT findings of pneumonia and the presence or absence of each type of aspiration were then examined. RESULTS: No significant correlations were observed between food aspiration and chest CT findings of pneumonia, whereas saliva aspiration and chest CT findings of pneumonia were significantly correlated. In addition, saliva aspiration was significantly associated with bronchial wall thickening (p < 0.01) and atelectasis (p < 0.05). CONCLUSIONS: Our findings in children suggest that: (1) the presence or absence of food aspiration detected by FEES evaluation has little correlation with pneumonia, and (2) the presence or absence of saliva aspiration may be an indicator of aspiration pneumonia risk.

[Perioperative Oral Management for Esophageal Cancer Patients].

Aspiration pneumonia, known as one of the most common postoperative complication after esophagectomy for esophageal cancer, can be critical profoundly affecting upon postoperative course of patients. Since oral bacteria can be one of causes for development of postoperative pneumonia, perioperative oral management has very important role in reducing morbidity and improving function of dysphagia. We started perioperative oral management as a team approach for patients undergoing esophageal surgery since 1997. In the present study, we are going to introduce details of these our efforts including reoperative evaluation of oral status, education and tutorship for patients, and oral treatment to reduce postoperative complications after esophagectomy of esophageal cancer.

Functional characterization of a new grapevine MYB transcription factor and regulation of proanthocyanidin biosynthesis in grapes.

A new regulator of proanthocyanidin (PA) biosynthesis in grapes was found by screening genes coordinately expressed with PA accumulation under different light conditions using a substantially improved method of serial analysis of gene expression (SuperSAGE). This R2R3-MYB transcription factor, VvMYBPAR, shows high protein sequence similarity with PA biosynthesis-regulating plant MYBs, such as VvMYBPA2 and TRANSPARENT TESTA2. Its transcript levels were relatively high in the skins of young berries, whereas the levels were higher in the seeds and at a maximum around veraison. In addition to its response to modified light conditions, the gene responded to abscisic acid application in the skins of cultured berries. Among the PA-specific branch genes, this transcript profile was not correlated with that of VvANR and VvLAR1 but was closely related to that of VvLAR2, suggesting different regulation of PA-specific branch genes from that of a known PA regulator, VvMYBPA2. The PA-specific regulation of VvMYBPAR was confirmed by VvMYBPAR constitutive expression in Arabidopsis in which the transgene specifically induced PA biosynthetic genes and resulted in PA accumulation in plants grown on sucrose-supplemented media to induce anthocyanin synthesis. A transient reporter assay using grapevine cells showed that VvMYBPAR activated the promoters on PA-specific branch genes and candidate genes associated with modification and transport of monomeric PA precursors, as well as the promoters of VvCHS3 and VvF3'5'Hd in the common flavonoid pathway, but not that of VvUFGT on the anthocyanin-specific branch. This new factor suggests the polygenic regulation of PA biosynthesis in grapes by closely related MYB transcription factors.

The efficacy of a lingual augmentation prosthesis for swallowing after a glossectomy: a clinical report.

The excision of malignant tongue tumors often produces tongue defects that can cause dysphagia. A palatal augmentation prosthesis is frequently used to treat such dysphagia. This report describes a patient who received a palatal augmentation prosthesis after a glossectomy for malignant cancer of the tongue; however, no improvement was noted in swallowing function. A lingual augmentation prosthesis was then applied to the mandible, which resulted in improved swallowing function.

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.

Essential role of Ubr11, but not Ubr1, as an N-end rule ubiquitin ligase in Schizosaccharomyces pombe.

The N-end rule pathway degrades proteins bearing a destabilization-inducing amino acid at the N-terminus. In this proteolytic system, Ubr ubiquitin ligases recognize and ubiquitylate substrates intended for degradation. Schizosaccharomyces pombe has two similar Ubr proteins, Ubr1 and Ubr11. Both proteins have unique roles in various cellular processes, although the ubr1∆ strain shows more severe defects. However, their involvement in the N-end rule pathway is unclear, and even the N-end rule pathway-dependent proteolytic activity has not been demonstrated in Sz. pombe. Here, we show that: (a) Sz. pombe has the N-end rule pathway in which only Ubr11, but not Ubr1, is responsible; and (b) the C-terminal fragment of the meiotic cohesin Rec8 (denoted as Rec8c) generated by separase-mediated cleavage is an endogenous substrate of the N-end rule pathway. Forced overexpression of stable Rec8c was deleterious in mitosis and caused a loss of the mini-chromosome. In unperturbed mitosis without overexpression, the rate of mini-chromosome loss was five-fold higher in the ubr11∆ strain. Since Rec8 is normally produced in meiosis, we examined whether meiosis and sporulation were affected in the ubr11∆ strain. In unperturbed meiosis, chromosome segregation occurred almost normally and viable spores were produced in the ubr11∆ cells, irrespective of the presence of undegraded endogenous Rec8c peptides.

Effect of anti-scatter grids on the image improvement factor in digital radiography for various phantom thicknesses and irradiation fields.

Digital radiography (DR) is used to acquire digital images with a consistent image brightness under different exposures and in the presence of various anti-scatter grids. This study effectively evaluates the image improvement factor and the conventional physical imaging properties, such as grid selectivity, contrast improvement ratio, and grid exposure factor. Various grids and acrylic phantoms of thicknesses 20 cm and 12 cm were used in this evaluation to simulate the pelvis and lumbar spine, and the cervical spine, respectively. Applied irradiation fields were adjusted according to the simulated body parts. Eight grids (four at 40 cm-1 strip frequency with grid ratios of 6:1, 8:1, 10:1, and 12:1, and four at 60 cm-1 strip frequency with grid ratios of 8:1, 10:1, 12:1, and 14:1) were used in this study. The grid selectivity, contrast improvement ratio, and grid exposure factor increased with higher grid ratios. At a constant grid ratio, these three parameters exhibited higher values at lower strip frequency (40 cm-1) than at higher strip frequency (60 cm-1). The change in the image improvement factor of the simulated cervical spine with respect to the grid was smaller than those of the simulated pelvis and lumbar spine. Our results suggested that the image improvement factor is a useful index for selecting grids according to object thickness at a constant exposure in DR systems.

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.

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.

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.

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.