General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Longitudinal Assessment of Quality of Life in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Proton Therapy and Volumetric Modulated Arc Therapy at Different Time Points.

PURPOSE: This retrospective cohort study aims to compare the quality of life (QoL) in patients with nasopharyngeal cancer (NPC) treated with intensity-modulated proton therapy (IMPT) versus volumetric modulated arc therapy (VMAT) at different time points. MATERIALS AND METHODS: We conducted a longitudinal assessment of QoL on 287 newly diagnosed NPC patients (IMPT: 41 and VMAT: 246). We collected outcomes of global QoL, functional QoL, C30 symptoms, and HN35 symptoms from EORTC QLQ-C30 and QLQ-HN35 questionnaires at pre-radiotherapy, during radiotherapy (around 40 Gy), 3 months post radiotherapy, and 12-months post radiotherapy (RT). The generalized estimating equation was utilized to interpret the group effect, originating from inherent group differences; time effect, attributed to RT effects over time; and interaction of the group and time effect. RESULTS: IMPT demonstrated superior mean dose reductions in 12 of the 16 organs at risk compared to VMAT, including a significant (>50%) reduction in the oral cavity and larynx. Both groups exhibited improved scores of global QoL, functional QoL, and C30 symptoms at 12 months post RT compared to the pre-RT status. Regarding global QoL and C30 symptoms, there was no interaction effect of group over time. In contrast, significant interaction effects were observed on functional QoL (p = 0.040) and HN35 symptoms (p = 0.004) during RT, where IMPT created an average of 7.5 points higher functional QoL and 10.7 points lower HN35 symptoms than VMAT. CONCLUSIONS: Compared to VMAT, dose reduction attributed to IMPT could translate into better functional QoL and HN35 symptoms, but the effect is time dependent and exclusively observed during the RT phase.

Cryptotanshinone regulates gut microbiota and PI3K-AKT pathway in rats to alleviate CUMS induced depressive symptoms.

Cryptotanshinone (CPT), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza, exhibits promising antidepressant properties. Employing a rat model subjected to Chronic Unpredictable Mild Stress (CUMS), behavioral analyses (open field experiment, elevated cross maze experiment, sugar water preference experiment, forced swimming experiment) and inflammatory factor assessments were conducted to assess the efficacy of CPT in alleviating depressive symptoms and inflammatory responses induced by CUMS. Moreover, 16 S rDNA analysis revealed alterations in the gut microbiota of rats exposed to both CUMS and CPT administration. Notably, CPT administration was found to mitigate harmful bacterial shifts associated with depression. Preliminary exploration of the molecular mechanism underlying CPT's antidepressant effects via transcriptomics analysis and molecular docking indicated that CPT might exert its influence by regulating the PI3K-AKT pathway. This study sheds light on the potential therapeutic role of CPT in managing depressive disorders, offering a comprehensive understanding of its impact on behavior, inflammation, gut microbiota, and molecular pathways.

Prognostic utility of neutrophil-to-albumin ratio in surgically treated oral squamous cell carcinoma.

BACKGROUND: We aimed to evaluate the prognostic significance of preoperative neutrophil-to-albumin ratio (NAR) in oral squamous cell carcinoma (OSCC). METHODS: A total of 622 patients with surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome-associated factors. RESULTS: The optimal cut-off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer-specific survival, and recurrence-free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all p < 0.05). The NAR-based nomogram accurately predicted OS (concordance index: 0.750). CONCLUSION: Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR-based nomogram can be a promising prognostic tool in clinical setting.

PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediated CSF2 transactivation: clinical and therapeutic relevance of amplification and nuclear entry.

Myxofibrosarcoma is genetically complex without established nonsurgical therapies. In public datasets, PAK1 was recurrently gained with mRNA upregulation. Using myxofibrosarcoma cells, we explored the oncogenic underpinning of PAK1 with genetic manipulation and a pan-PAK inhibitor (PF3758309). Myxofibrosarcoma specimens were analyzed for the levels of PAK1, phospho-PAKT423, CSF2 and microvascular density (MVD) and those of PAK1 gene and mRNA. PAK1-expressing xenografts were assessed for the effects of PF3758309 and CSF2 silencing. Besides pro-proliferative and pro-migrator/pro-invasive attributes, PAK1 strongly enhanced angiogenesis in vitro, which, not phenocopied by PAK2-4, was identified as CSF2-mediated using antibody arrays. PAK1 underwent phosphorylation at tyrosines153,201,285 and threonine423 to facilitate nuclear entry, whereby nuclear PAK1 bound STAT5B to co-transactivate the CSF2 promoter, increasing CSF2 secretion needed for angiogenesis. Angiogenesis driven by PAK1-upregulated CSF2 was negated by CSF2 silencing, anti-CSF2, and PF3758309. Clinically, overexpressed whole-cell phospho-PAKT423, related to PAK1 amplification, was associated with increased grades, stages, and PAK1 mRNA, higher MVD, and CSF2 overexpression. Overexpressed whole-cell phospho-PAKT423 and CSF2 independently portended shorter metastasis-free survival and disease-specific survival, respectively. In vivo, both CSF2 silencing and PF3758309 suppressed PAK1-driven tumor proliferation and angiogenesis. Conclusively, the nuclear entry of overexpressed/activated PAK1 endows myxofibrosarcomas with pro-angiogenic function, highlighting the vulnerable PAK1/STAT5B/CSF2 regulatory axis.

Evaluation of Sinonasal Outcome Test (SNOT-22) Domains in the Assessment of the Quality of Life in Patients with Nasopharyngeal Carcinoma.

Background: Few instruments are available for assessing the otorhinologic-related quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients. Therefore, we evaluated whether the 22-item Sinonasal Outcome Test (SNOT-22) could be applied to these patients. Methods: Patients diagnosed with NPC, who had been treated with standard protocol and followed up in our institute between 2019 and 2022, were invited to join the cross-sectional study during their clinic visits. All participants completed the SNOT-22 and Eustachian Tube Dysfunction Questionnaire-7 once they were recruited. Confirmatory factor analysis (CFA) was performed to decide the most suitable model for the underlying SNOT-22 subdomains, along with various validity and reliability tests. Results: We identified a total of 275 patients, with 84 (30.5%) women and 191 (69.5%) men. The mean age was 54.1 years (standard deviation: 11.2). Among these patients, 171 (62.1%) were in late stages, and 260 (94.5%) received chemoradiotherapy as treatment. The median interval between primary RT treatment and questionnaire completion was 50 months (interquartile range: 29-93). CFA supported a five-factor model for the SNOT-22 for NPC patients, including nasal, ear/facial, sleep, function, and emotion domains. The internal consistency and test-retest reliability of the SNOT-22 domain score were good. In addition, known-group validity was good for the SNOT-22 total score and domain scores according to the disease recurrence status. Conclusion: Psychometric analyses supported the reliability and validity of a five-domain SNOT-22 for assessing otorhinologic-related QOL in NPC patients.

ASXL3 gene mutations inhibit cell proliferation and promote cell apoptosis in mouse cardiomyocytes by upregulating lncRNA NONMMUT063967.2.

Congenital heart disease (CHD) is a serious condition with unknown etiology. In a recent study, a compound heterozygous mutation (c.3526C > T [p.Arg1176Trp] and c.4643A > G [p.Asp1548Gly]) in the ASXL3 gene was identified, which is associated with CHD. This mutation was overexpressed in HL-1 mouse cardiomyocyte cells, leading to increased cell apoptosis and decreased cell proliferation. However, whether this effect is mediated by long noncoding RNAs (lncRNAs) is yet to be determined. We identified the differences among lncRNA and mRNA profiles in mouse heart tissues using sequencing to explore this issue. We detected HL-1 cell proliferation and apoptosis through CCK8 and flow cytometry. Fgfr2, lncRNA, and Ras/ERK signaling pathway expressions were evaluated using quantitative real time polymerase chain reaction (qRT-PCR) and western blot (WB) assays. We also conducted functional investigations by silencing lncRNA NONMMUT063967.2. The sequencing revealed significant changes in lncRNA and mRNA profiles, with the expression of lncRNA NONMMUT063967.2 being significantly promoted in the ASXL3 gene mutations group (MT) while the expression of Fgfr2 being downregulated. The in vitro experiments showed that ASXL3 gene mutations inhibited the proliferation of cardiomyocytes and accelerated cell apoptosis by promoting the expression of lncRNAs (NONMMUT063967.2, NONMMUT063918.2, and NONMMUT063891.2), suppressing the formation of FGFR2 transcripts, and inhibiting the Ras/ERK signaling pathway. The decrease in FGFR2 had the same effect on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes as ASXL3 mutations. Further mechanistic studies revealed that suppression of lncRNA NONMMUT063967.2 and overexpression of FGFR2 reversed the effects of the ASXL3 mutations on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes. Therefore, ASXL3 mutation decreases FGFR2 expression by upregulating lncRNA NONMMUT063967.2, inhibiting cell proliferation and promoting cell apoptosis in mouse cardiomyocytes.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Blue Nevus Hidden within the Nevus of Ota.

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.

Low p16 Cytoplasmic Staining Predicts Poor Treatment Outcome in Patients with p16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving TPF Induction Chemotherapy.

Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in HNSCC prognosis. A total of 195 HNSCC patients who received docetaxel, cisplatin, and 5-fluouracil (TPF) induction chemotherapy followed by chemoradiotherapy were enrolled. The status of p16 cytoplasmic staining was determined using immunohistochemistry. The median follow-up was 26.0 months for the whole study population and 90.3 months for 51 living survivors. p16 cytoplasmic staining was low in 108 patients and high in 87 patients. Low expression of p16 cytoplasmic staining and primary tumor location in the oral cavity were both independent factors indicating a worse response rate to TPF induction chemotherapy in the univariate and multivariate analyses. The logistic regression model also showed that low expression of p16 cytoplasmic staining and clinical N2-3 status were independent prognostic factors for worse progression-free survival and overall survival. Our study showed that p16 cytoplasmic staining could predict the treatment response to TPF induction chemotherapy and is an independent prognostic factor of survival in HNSCC.

Acute radiation dermatitis among patients with nasopharyngeal carcinoma treated with proton beam therapy: Prognostic factors and treatment outcomes.

A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This observational study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Treatment of ARD included topical corticosteroid alone in 24 (42.1%) patients, topical corticosteroid plus silver sulfadiazine in 33 (57.9%) patients, and non-adhering silicone dressing to cover severe skin wound area in 25 (43.8%) patients. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking (odds ratio [OR]: 5.2, 95% confidence interval [CI]: 1.3-18.8, P = .012) and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6-15.4, P = .006) as independent predictors of grade 2 and 3 ARD. The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid, silver sulfadiazine, and non-adhering silicone dressing are effective for treating ARD induced by PBT.

Current status of animal models of cataract classified by etiology / 国际眼科杂志(Guoji Yanke Zazhi)

Cataract is one of the major causes of vision loss and even blindness in patients, and surgery is the only effective method to treat it. The pathogenesis and precaution of cataract remain hot issues in ophthalmological research. With the maturation of biotechnology in recent years, modeling methods and species of experimental animals have become more diverse, which are still the mainstay of cataract mechanism research. However, the ideal animal model of cataract has yet to be constructed due to the complexity of human cataract etiology. Herein, the modeling principles, in vivo or in vitro modeling methods, characteristics, and existing problems of animal models of cataract are summarized according to etiology, providing the theoretical foundation for the construction of a comprehensive animal model that more closely resembles the human cataract.

Glomuvenous malformation: a clinicopathological analysis of 31 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.

The Prognostic Value of Preoperative Albumin-to-Alkaline Phosphatase Ratio on Survival Outcome for Patients With Locally Advanced Oral Squamous Cell Carcinoma.

Background: This retrospective cohort study was to assess the prognostic value of preoperative albumin-to-alkaline phosphatase ratio (AAPR) on survival outcome for patients with locally advanced oral squamous cell carcinoma (LAOSCC). Methods: A total of 250 patients with LAOSCC receiving upfront radical surgery at a single institute from January 2008 to December 2017 were enrolled. The primary endpoint was the survival predictability of preoperative AAPR on the 5-year overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Cox proportional hazards model was used for survival analysis. The X-tile software was used to estimate the optimal cut-off value of preoperative AAPR on survival prediction. A predictive nomogram incorporating the clinicopathological factors on OS was further generated. Results: The 5-year OS, CSS, and DFS rates were 68.6%, 79.7%, and 61.7%, respectively. The optimal cut-off of preoperative AAPR to predict the 5-year OS was observed to be 0.51. For those with preoperative AAPR≧0.51, the 5-year OS, CSS, and DFS were statistically significantly superior to those with preoperative AAPR<0.51 (OS: 76.1% vs 48.5%, P < .001; CSS: 84.3% vs 66.4%, P = .005; DFS: 68.9% vs 42.6%, P < .001). In Cox model, we observed that preoperative AAPR<0.51 was a significantly negative prognosticator of OS (HR: 2.22, 95% CI: 1.466-3.361, P < .001), CSS (HR: 2.037, 95% CI: 1.16-3.578, P = .013), and DFS (HR: 1.756, 95% CI: 1.075-2.868, P = .025). After adding the variable of preoperative AAPR, the c-index of the predictive nomogram incorporating assorted clinicopathological factors increases from 0.663 to 0.692 for OS. Conclusion: Our results suggest that preoperative AAPR serves as an independent survival predictor for patients with LAOSCC. The nomogram incorporating preoperative AAPR and various clinicopathological features may be a convenient tool to estimate the mortality risk for patients with LAOSCC.

The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

Effect of glycated hemoglobin A1c on the survival of patients with oral squamous cell carcinoma: A multi-institutional database cohort study.

Objectives: Few studies have evaluated the impact of blood glucose levels on cancer prognosis. We investigated the association between hemoglobin A1c (HbA1c) and survival in oral squamous cell carcinoma (OSCC) patients. Materials and Methods: A 19-year retrospective cohort study of OSCC patients was performed using the Chang Gung Research Database to identify and enroll 7279 patients diagnosed with OSCC between January 2001 and June 2020. A total of 3600 patients were recruited after performing 1:2 frequency-matching between patients with DM and non-DM. A Cox's regression model was used to evaluate the relative hazards of all-cause mortality (ACM) and disease-specific mortality (DSM) in relation to HbA1c. Results: An unadjusted Cox's regression model indicated that DM, in addition to high levels of HbA1c, were statistically prognostic of poor survival. An adjusted hazard ratio (aHR) of HbA1c ≥ 8% interval at the initial diagnosis of OSCC was statistically higher for DSM (1.25 to 2.24) compared to the non-DM group in different regression models. Considering the effect of sustained HbA1c control in 699 patients, the aHR of mean HbA1c ≥ 9% interval was statistically higher for ACM (1.78 to 2.13) compared to the reference group (7% ≤ HbA1c< 8%). In addition, increased hazards of ACM (2.09 to 2.18) and DSM (2.20 to 2.41) were consistently observed in the highest quartiles of average real variability of HbA1c. Conclusion: Poor and unstable control of HbA1c could strongly predict the risks of mortality in OSCC patients with DM.

Salvage Radiotherapy Plus Androgen Deprivation Therapy for High-Risk Prostate Cancer with Biochemical Failure after High-Intensity Focused Ultrasound as Primary Treatment.

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6−12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.

Dosimetric Parameters Related to Acute Radiation Dermatitis of Patients with Nasopharyngeal Carcinoma Treated by Intensity-Modulated Proton Therapy.

Background: Growing patients with nasopharyngeal carcinoma (NPC) were treated with intensity-modulated proton therapy (IMPT). However, a high probability of severe acute radiation dermatitis (ARD) was observed. The objective of the study is to investigate the dosimetric parameters related to ARD for NPC patients treated with IMPT. Methods: Sixty-two patients with newly diagnosed NPC were analyzed. The ARD was recorded based on the criteria of Common Terminology Criteria for Adverse Events version 4.0. Logistic regression model was performed to identify the clinical and dosimetric parameters related to ARD. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models. Results: The maximum ARD grade was 1, 2, and 3 in 27 (43.5%), 26 (42.0%), and 9 (14.5%) of the patients, respectively. Statistically significant differences (p < 0.01) in average volume to skin 5 mm with the respective doses were observed in the range 54−62 Cobalt Gray Equivalent (CGE) for grade 2 and 3 versus grade 1 ARD. Smoking habit and N2-N3 status were identified as significant predictors to develop grade 2 and 3 ARD in clinical model, and V58CGE to skin 5 mm as an independent predictor in dosimetric model. After adding the variable of V58CGE to the metric incorporating two parameters of smoking habit and N status, the AUC value of the metric increases from 0.78 (0.66−0.90) to 0.82 (0.72−0.93). The most appropriate cut-off value of V58CGE to skin 5 mm as determined by ROC curve was 5.0 cm3, with a predicted probability of 54% to develop grade 2 and 3 ARD. Conclusion: The dosimetric parameter of V58CGE to skin 5 mm < 5.0 cm3 could be used as a constraint in treatment planning for NPC patients treated by IMPT.

Prognostic Value of Pathologically Positive Nodal Number in p16-Negative Oropharyngeal and Hypopharyngeal Squamous Cell Carcinoma with pN3b Status.

In this study, we aimed to investigate the prognostic value of the number of pathologically positive nodes (pN+) in p16-negative oropharyngeal (OPSCC) and hypopharyngeal (HPSCC) squamous cell carcinoma cases with pN3b status after surgery. We reviewed the clinical and pathological features of 120 newly diagnosed p16-negative OPSCC and HPSCC patients with pN3b status after radical surgery. The primary endpoints were the 5-year overall survival (OS), cancer-specific survival (CSS), and their prognostic factors. We used the Cox proportional hazards model for survival analysis. We generated predictive nomograms that incorporated the clinicopathological factors of OS and CSS. The 5-year OS and CSS rates were 44.1% and 59.1%, respectively. The optimal number of pN+ to predict the 5-year OS and CSS was pN+ = 3. In the Cox model, we observed that pN+ ≥ 3 was a significantly negative predictor of OS (HR: 1.9, 95% CI: 1.1-3.2, p = 0.021) and CSS (HR: 2.3; 95% CI: 1.2-4.6; p = 0.015). After adding the pN+ variable, the c-index of the predictive nomogram incorporating assorted clinicopathological factors increased from 0.66 to 0.689 for OS and from 0.713 to 0.75 for CSS. The results highlight the prognostic value of the pN+ number in p16-negative OPSCC and HPSCC patients with pN3b status.

The Impact of Weight Loss during Chemoradiotherapy for Unresectable Esophageal Cancer: Real-World Results.

Weight loss is a common phenomenon presented in unresectable esophageal cancer (EC) patients during their definitive chemoradiotherapy (dCRT) treatment course. This study explored the prognostic value of weight changes during dCRT in unresectable EC patients. From 2009 to 2017, 69 cT4b thoracic EC patients undergoing complete curative dCRT without baseline malnutrition were included. Clinical factors were analyzed via the Cox proportional hazards model and survival was analyzed by the Kaplan−Meier method. During dCRT, the median weight loss percentage was 5.51% (IQR = 2.77−8.85%), and the lowest body weight was reached at 35 days (IQR = 23−43 days). Median OS of these patients was 13.5 months. Both univariate and multivariate analysis demonstrated that weight loss ≤ 4% during dCRT was significantly associated with superior OS with a hazard ratio of 2.61 (95% CI: 1.40−4.85, p = 0.002). The median OS for patients with weight loss ≤ 4% and >4% during dCRT was 59.6 months and 9.7 months, respectively (p = 0.001). Our study demonstrated that weight loss ≤ 4% during dCRT course is a favorable prognostic factor for cT4b EC patients. This index could serve as a nutrition support reference for unresectable EC patients receiving dCRT in the future.