Photodynamic therapy using talaporfin sodium for non-totally resectable malignant glioma.

BACKGROUND: For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. METHODS: Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery. RESULTS: In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months. CONCLUSIONS: PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions.

Exercise Stress Echocardiography-Based Phenotyping of Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome requiring improved phenotypic classification. Previous studies have identified subphenotypes of HFpEF, but the lack of exercise assessment is a major limitation. This study sought to identify distinct pathophysiologic clusters of HFpEF based on clinical characteristics, and resting and exercise assessments. METHODS: A total of 265 patients with HFpEF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Cluster analysis was performed by the K-prototype method with 21 variables (10 clinical and resting echocardiographic variables and 11 exercise echocardiographic parameters). Pathophysiological features, exercise tolerance, and prognosis were compared among phenogroups. RESULTS: Three distinct phenogroups were identified: Phenogroup 1 (n=112, 42%) was characterized by preserved biventricular systolic reserve and cardiac output augmentation. Phenogroup 2 (n=58, 22%) was characterized by a high prevalence of atrial fibrillation, increased pulmonary arterial and right atrial pressures, depressed RV systolic functional reserve, and impaired right ventricular-pulmonary artery coupling during exercise. Phenogroup 3 (n=95, 36%) was characterized by the smallest body mass index, ventricular and vascular stiffening, impaired LV diastolic reserve, and worse exercise capacity. Phenogroups 2 and 3 had higher rates of composite outcomes of all-cause mortality or HF events than phenogroup 1 (log-rank p=0.02). CONCLUSION: Exercise echocardiography-based cluster analysis identified three distinct phenogroups of HFpEF, with unique exercise pathophysiological features, exercise capacity, and clinical outcomes.

Reductive N-Alkylation of Amines with Ketones Using Heterogeneous Polysilane-Palladium Catalysts under Continuous-Flow Conditions.

This work reports a continuous-flow reductive N-alkylation of amines with ketones using molecular hydrogen. The reaction, performed with highly active polysilane-modified heterogeneous palladium catalysts, enables the efficient synthesis of diversely substituted amines under mild flow conditions. The developed catalyst exhibits sustained activity for 5 days (turnover number of >2400). Moreover, the utility of the method is demonstrated by the synthesis of a key intermediate of the active pharmaceutical ingredient teneligliptin.

Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis.

Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS-genes in the mevalonate pathway-cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells.

Optimal timing of electrical cardioversion for acute decompensated heart failure caused by atrial arrhythmias: The earlier, the better?

The optimal timing for electrical cardioversion (ECV) in acute decompensated heart failure (ADHF) with atrial arrhythmias (AAs) is unknown. Here, we retrospectively evaluated the impact of ECV timing on SR maintenance, hospitalization duration, and cardiac function in patients with ADHF and AAs. Between October 2017 and December 2022, ECV was attempted in 73 patients (62 with atrial fibrillation and 11 with atrial flutter). Patients were classified into two groups based on the median number of days from hospitalization to ECV, as follows: early ECV (within 8 days, n = 38) and delayed ECV (9 days or more, n = 35). The primary endpoint was very short-term and short-term ECV failure (unsuccessful cardioversion and AA recurrence during hospitalization and within one month after ECV). Secondary endpoints included (1) acute ECV success, (2) ECVs attempted, (3) periprocedural complications, (4) transthoracic echocardiographic parameter changes within two months following successful ECV, and (5) hospitalization duration. ECV successfully restored SR in 62 of 73 patients (85%), with 10 (14%) requiring multiple ECV attempts (≥ 3), and periprocedural complications occurring in six (8%). Very short-term and short-term ECV failure occurred without between-group differences (51% vs. 63%, P = 0.87 and 61% vs. 72%, P = 0.43, respectively). Among 37 patients who underwent echocardiography before and after ECV success, the left ventricular ejection fraction (LVEF) significantly increased (38% [31-52] to 51% [39-63], P = 0.008) between admission and follow-up. Additionally, hospital stay length was shorter in the early ECV group than in the delayed ECV group (14 days [12-21] vs. 17 days [15-26], P < 0.001). Hospital stay duration was also correlated with days from admission to ECV (Spearman's ρ = 0.47, P < 0.001). In clinical practice, early ECV was associated with a shortened hospitalization duration and significantly increased LVEF in patients with ADHF and AAs.

Comprehensive genetic profiling reveals frequent alterations of driver genes on the X chromosome in extranodal NK/T-cell lymphoma.

Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. Here, we performed comprehensive genetic analysis of 177 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNAs), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1. Among them, CD274 (24%) was the most frequently altered, followed by TP53 (20%), CDKN2A (19%), ARID1A (15%), HLA-A (15%), BCOR (14%), and MSN (14%). Chromosome X (chrX) losses were the most common arm-level CNAs in females (~40%), and alterations of four X-linked driver genes (MSN, BCOR, DDX3X, and KDM6A) were more frequent in males and females harboring chrX losses. Among X-linked drivers, MSN was the most recurrently altered, and its expression was lost in approximately one-third of cases using immunohistochemical analysis. Functional studies of human cell lines demonstrated that MSN disruption promoted cell proliferation and NF-κB activation. Moreover, MSN inactivation increased sensitivity to NF-κB inhibition in vitro and in vivo. In addition, recurrent deletions were observed at the origin of replication in the EBV genome (6%). Finally, by integrating the 34 drivers and 19 significant arm-level CNAs, non-negative matrix factorization and consensus clustering identified two molecular groups with different genetic features and prognosis irrespective of clinical prognostic factors. Together, these findings could help improve diagnostic and therapeutic strategies in ENKTCL.

Relationship between onset of trunk muscle activities and pelvic kinematics in individuals with and without chronic low back pain.

BACKGROUND: Lumbopelvic movement patterns during prone hip extension has been proposed as a clinical screening method for trunk muscle dysfunction in patients with chronic low back pain (CLBP). However, correlations between trunk muscle onset and pelvic kinematics have not been investigated. OBJECTIVE: To examine the correlation between trunk muscle onset and pelvic kinematics during prone hip extension in participants with CLBP. METHODS: Fifteen patients with CLBP and 15 healthy individuals participated. We evaluated the muscle activities of the lumbar multifidus, the longissimus, and the semitendinosus via electromyogram and the displacement angles of the pelvic tilt, oblique and rotation. RESULTS: The onset of the multifidus at the ipsilateral side of hip extension was significantly delayed in the patients with CLBP compared to the control group (P< 0.001). The onset of the ipsilateral multifidus in the control group was significantly correlated with increased anterior pelvic tilt angle (P= 0.019, r= 0.597), whereas no significant correlation was observed in the CLBP group (P= 0.810, r=-0.068). CONCLUSION: The results suggest that pelvic kinematics during prone hip extension does not predict the delayed trunk muscle onset in patients with CLBP.

Efficacy of interstitial photodynamic therapy using talaporfin sodium and a semiconductor laser for a mouse allograft glioma model.

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.

Role of stereotactic radiosurgery for recurrent skull base acinic cell carcinoma: illustrative case.

BACKGROUND: Acinic cell carcinomas (AcCCs), rare malignancies of the salivary glands, often recur and metastasize, particularly in the skull base. Conventional radical resection can be invasive for skull base AcCCs adjacent to cranial nerves and major vasculature, and the effectiveness of stereotactic radiosurgery (SRS) as an alternative is not well established. OBSERVATIONS: This case report details the application of SRS for recurrent skull base AcCCs. A 71-year-old male with a history of resection for a right mandibular AcCC 23 years earlier experienced tumor recurrence involving the right cavernous sinus and nasal cavity. He underwent endoscopic transnasal surgery followed by SRS targeting different tumor locations-the cavernous sinus to the pterygopalatine fossa, maxillary sinus, and clivus-each with a prescribed dose of 20 Gy to the 40% to 50% isodose line. After the first skull base metastasis, additional sessions of localized SRS after endoscopic surgery led to a 12-year survival without sequela. LESSONS: This is a report indicating that SRS for skull base AcCCs can achieve favorable local control, functional preservation, and long-term survival. SRS may be suitable for skull base AcCC given the lesion's tendency toward multiple local recurrences. Further investigation is needed to validate the treatment's efficacy.

Trunk Muscle Activity and Ratio of Local Muscle to Global Muscle Activity during Supine Bridge Exercises under Unstable Conditions in Young Participants with and without Chronic Low Back Pain.

Core exercises on an unstable surface increase trunk muscle activity, especially for local muscle groups. Therefore, there is a possibility that exercises on an unstable surface would be effective in the rehabilitation of non-specific chronic low back pain (NSCLBP). The present study assessed trunk muscle activities during bridge exercise on the floor and two kinds of unstable surfaces, i.e., a balance ball and the BOSU, for individuals with and without NSCLBP. This study enrolled 17 and 18 young participants with and without NSCLBP, respectively. In the balance ball condition, both groups showed a significant increase in erector spinae activity compared to the floor condition, and the increase in activity was significantly greater in the NSCLBP group than in the control group (p = 0.038). On the other hand, neither group showed significant changes in trunk muscle activities in the BOSU condition compared to those in the floor condition. The control group showed a significant increase in internal oblique/transversus abdominis activity under the balance ball condition (p = 0.020), whereas there were no significant changes in these muscle activities between the balance ball and floor conditions in the NSCLBP group. The present study showed that participants with NSCLBP significantly increased muscle activity of the erector spinae, one of the global back muscles, on the balance ball in spite of small effects on muscle activity of the internal oblique/transversus abdominis, which is one of the local abdominal muscles. Therefore, attention should be paid to the application of bridge exercises on the balance ball for individuals with NSCLBP.

Cellular senescence and wound healing in aged and diabetic skin.

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects.

A New Non-Obese Steatohepatitis Mouse Model with Cardiac Dysfunction Induced by Addition of Ethanol to a High-Fat/High-Cholesterol Diet.

Non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with cardiovascular-related mortality, leading to a higher mortality rate compared to the general population. However, few reports have examined cardiovascular events in non-obese MASLD mouse models. In this study we created a mouse model to mimic this condition. In this study involving seven-week-old C57BL/6J male mice, two dietary conditions were tested: a standard high-fat/high-cholesterol diet (STHD-01) and a combined diet of STHD-01 and ethanol. Over periods of 6 and 12 weeks, we analyzed the effects on liver and cardiac tissues using various staining techniques and PCR. Echocardiography and blood tests were also performed to assess cardiac function and liver damage. The results showed that mice on the ethanol-supplemented STHD-01 diet developed signs of steatohepatitis and cardiac dysfunction, along with increased sympathetic activity, as early as 6 weeks. At 12 weeks, more pronounced exacerbations accompanied with cardiac dilation, advanced liver fibrosis, and activated myocardial fibrosis with sympathetic activation were observed. This mouse model effectively replicated non-obese MASLD and cardiac dysfunction over a 12-week period using a combined diet of STHD-01 and ethanol. This dietary approach highlighted that both liver inflammation and fibrosis, as well as cardiac dysfunction, could be significantly worsened due to the activation of the sympathetic nervous system. Our results indicate that alcohol, even when completely metabolized on the day of drinking, exacerbates the progression of non-obese MASLD and cardiac dysfunction.

Pan-Cancer Comparative and Integrative Analyses of Driver Alterations Using Japanese and International Genomic Databases.

Using 48,627 samples from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), we present a pan-cancer landscape of driver alterations and their clinical actionability in Japanese patients. Comparison with White patients in Genomics Evidence Neoplasia Information Exchange (GENIE) demonstrates high TP53 mutation frequencies in Asian patients across multiple cancer types. Integration of C-CAT, GENIE, and The Cancer Genome Atlas data reveals many cooccurring and mutually exclusive relationships between driver mutations. At pathway level, mutations in epigenetic regulators frequently cooccur with PI3K pathway molecules. Furthermore, we found significant cooccurring mutations within the epigenetic pathway. Accumulation of mutations in epigenetic regulators causes increased proliferation-related transcriptomic signatures. Loss-of-function of many epigenetic drivers inhibits cell proliferation in their wild-type cell lines, but this effect is attenuated in those harboring mutations of not only the same but also different epigenetic drivers. Our analyses dissect various genetic properties and provide valuable resources for precision medicine in cancer. SIGNIFICANCE: We present a genetic landscape of 26 principal cancer types/subtypes, including Asian-prevalent ones, in Japanese patients. Multicohort data integration unveils numerous cooccurring and exclusive relationships between driver mutations, identifying cooccurrence of multiple mutations in epigenetic regulators, which coordinately cause transcriptional and phenotypic changes. These findings provide insights into epigenetic regulator-driven oncogenesis. This article is featured in Selected Articles from This Issue, p. 695.

Assessment of mediastinal shift angles in congenital pulmonary airway malformation: a new fetal magnetic resonance imaging indicator of congenital lung disease.

BACKGROUND: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. OBJECTIVE: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. MATERIALS AND METHODS: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. RESULTS: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). CONCLUSION: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI.

Sodium-glucose co-transporter 2 inhibitors in acute heart failure: real-world prescription trends and outcomes analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited. METHODS AND RESULTS: We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n = 289) and a non-SGLT2i group (n = 819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366 days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P < 0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n = 413), HF with mildly reduced EF (n = 226), and HF with preserved EF (n = 466) (log-rank test; P = 0.044, P = 0.013, and P = 0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P < 0.001). This association was also significant in the LVEF subgroups (P = 0.005, P = 0.032, and P = 0.004, respectively). CONCLUSIONS: The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF.

Ultra-high combined positive score and high serum albumin are favorable prognostic biomarkers for immune checkpoint inhibitors in head and neck squamous cell carcinoma.

BACKGROUND: Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. METHODS: We prospectively measured the combined positive score (CPS) and administered ICI to patients with RMHNSCC. RESULTS: Of 51 patients, 23 patients had a CPS <20 and 12 patients (23.5%) had a CPS ≥90. CPS showed a negative correlation with serum albumin. Survival analysis showed a 2-year survival rate of 24.1%. In multivariate analysis, CPS ≥90 (HR 0.3026, p = 0.02614) and albumin >3.5 (HR 0.3463, p = 0.01354) were the significant factors and plus chemotherapy (HR 0.4648, p = 0.07632) was not significant. Seven patients (14%) with CPS ≥90 and albumin >3.5 showed a 2-year survival rate of 66. 7%. CONCLUSIONS: CPS ≥90 and albumin >3.5 cases are a subgroup of RMHNSCC that respond extremely well to ICI.

Transverse Cervical Artery for Head and Neck Reconstruction with Free Jejunal Flaps: A Retrospective Study of Computed Tomography Angiography.

BACKGROUND: The transverse cervical artery is less commonly used than other external carotid arteries as a recipient vessel. Therefore, we aimed to compare the utility of the transverse cervical artery as a recipient vessel with that of the external carotid artery system for microvascular head and neck reconstruction by quantitative analysis of dynamic-enhanced computed tomography. METHODS: Fifty-one consecutive patients who underwent free jejunum transfer following total pharyngolaryngectomy between January 2017 and December 2020 were retrospectively reviewed. Ninety-four pairs of the diameters of the transverse cervical artery, superior thyroid artery, and lingual artery, measured via computed tomography angiography, were analyzed. Operative outcomes were compared between the following groups based on the recipient artery: transverse cervical artery (n = 27), superior thyroid artery (n = 17), and other artery (n = 7) groups. RESULTS: In the analysis of the computed tomography angiography, nine transverse cervical arteries (9.6%) could not be identified. However, the percentage was significantly lower than the percentage of superior thyroid arteries (20.2%) and lingual arteries (18.1%) (p < 0.01). Among the identified vessels, the transverse cervical arteries (2.09 ± 0.41 mm) and the lingual arteries (1.97 ± 0.40 mm) were significantly larger than the superior thyroid arteries (1.70 ± 0.36 mm) in diameter at the commonly used level (p < 0.01). Multivariate analysis revealed that prior radiation therapy was not an independent factor significantly affecting transverse cervical artery diameter (p = 0.17). Intraoperative anastomotic revision was required in only two cases of the superior thyroid artery. CONCLUSION: The transverse cervical artery can offer a larger caliber and more reliable candidate than the superior thyroid artery for a recipient artery. More liberal use of the transverse cervical artery may improve the safety of microsurgical head and neck reconstruction.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:228-235, 2024.