Development of a risk prediction model for radiation dermatitis following proton radiotherapy in head and neck cancer using ensemble machine learning.

PURPOSE: This study aims to develop an ensemble machine learning-based (EML-based) risk prediction model for radiation dermatitis (RD) in patients with head and neck cancer undergoing proton radiotherapy, with the goal of achieving superior predictive performance compared to traditional models. MATERIALS AND METHODS: Data from 57 head and neck cancer patients treated with intensity-modulated proton therapy at Kaohsiung Chang Gung Memorial Hospital were analyzed. The study incorporated 11 clinical and 9 dosimetric parameters. Pearson's correlation was used to eliminate highly correlated variables, followed by feature selection via LASSO to focus on potential RD predictors. Model training involved traditional logistic regression (LR) and advanced ensemble methods such as Random Forest and XGBoost, which were optimized through hyperparameter tuning. RESULTS: Feature selection identified six key predictors, including smoking history and specific dosimetric parameters. Ensemble machine learning models, particularly XGBoost, demonstrated superior performance, achieving the highest AUC of 0.890. Feature importance was assessed using SHAP (SHapley Additive exPlanations) values, which underscored the relevance of various clinical and dosimetric factors in predicting RD. CONCLUSION: The study confirms that EML methods, especially XGBoost with its boosting algorithm, provide superior predictive accuracy, enhanced feature selection, and improved data handling compared to traditional LR. While LR offers greater interpretability, the precision and broader applicability of EML make it more suitable for complex medical prediction tasks, such as predicting radiation dermatitis. Given these advantages, EML is highly recommended for further research and application in clinical settings.

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.

Association of different cell types and inflammation in early acne vulgaris.

Acne vulgaris, one of the most common skin diseases, is a chronic cutaneous inflammation of the upper pilosebaceous unit (PSU) with complex pathogenesis. Inflammation plays a central role in the pathogenesis of acne vulgaris. During the inflammatory process, the innate and adaptive immune systems are coordinately activated to induce immune responses. Understanding the infiltration and cytokine secretion of differential cells in acne lesions, especially in the early stages of inflammation, will provide an insight into the pathogenesis of acne. The purpose of this review is to synthesize the association of different cell types with inflammation in early acne vulgaris and provide a comprehensive understanding of skin inflammation and immune responses.

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.

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.

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.

Automatic identification of benign pigmented skin lesions from clinical images using deep convolutional neural network.

OBJECTIVE: We aimed to develop a computer-aided detection (CAD) system for accurate identification of benign pigmented skin lesions (PSLs) from images captured using a digital camera or a smart phone. METHODS: We collected a total of 12,836 clinical images which had been classified and location-labeled for training and validating. Four models were developed and validated; you only look once, v4 (YOLOv4), you only look once, v5 (YOLOv5), single shot multibox detector (SSD) and faster region-based convolutional neural networks (Faster R-CNN). The performance of the models was compared with three trained dermatologists, respectively. The accuracy of the best model was further tested and validated using smartphone-captured images. RESULTS: The accuracies of YOLOv4, YOLOv5, SSD and Faster R-CNN were 0.891, 0.929, 0.852 and 0.874, respectively. The precision, sensitivity and specificity of YOLOv5 (the best model) were 0.956, 0.962 and 0.952, respectively. The accuracy of YOLOv5 model for images captured using a smart-phone was 0.905. The CAD based YOLOv5 system can potentially be used in clinical identification of PSLs. CONCLUSION: We developed and validated a CAD system for automatic identification of benign PSLs using digital images. This approach may be used by non-dermatologists to easily diagnose by taking a photo of skin lesion and guide on management of PSLs.

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.

The Radiation Dose to the Left Supraclavicular Fossa is Critical for Anastomotic Leak Following Esophagectomy - A Dosimetric Outcome Analysis.

Purpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50-50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing. We performed cervical anastomosis directly inside the left supraclavicular fossa (SCF), the irradiation target for esophageal cancer. The significance of radiation injury in patients with cervical anastomotic leak (AL) remains unclear. Thus, we assessed the influence of radiation on cervical AL in patients undergoing preoperative CCRT followed by esophagectomy. Patients and Methods: We defined the SYC zone, a portion of the region overlapping the left SCF. The radiation dose to the SYC zone was analyzed and correlated with AL in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were administered preoperative CCRT (radiation dose with 50-50.4 Gy/25-28 Fx to the primary esophageal tumor) followed by esophagectomy between October 2009 and January 2018. Receiver operating characteristic curve analysis and logistic regression were used to identify the optimal radiation factor to predict AL and the cutoff value. Results: The optimal radiation factor to predict AL was the mean dose to the SYC zone (area under the curve (AUC)=0.642), and the cutoff point of the mean dose was 48.55 Gray (Gy). For a mean SYC zone dose ≥48.55 Gy, the AL risk was sevenfold greater than that for <48.55 Gy (OR = 7.805; 95% CI: 1.184 to 51.446; P value = 0.033). Conclusion: Recognizing the SYC zone as an organ at risk and performing radiation evaluation are meaningful. A reduced mean dose of the SYC zone below 48.55 Gy results in a lower cervical AL rate following esophagectomy.

Prospective Evaluation of Taste Function in Patients With Head and Neck Cancer Receiving Intensity-Modulated Radiotherapy.

Importance: The majority of the patients with head and neck cancer (HNC) experience taste dysfunction (TD) during or after radiotherapy (RT). However, prospectively collected data for taste dysfunction have been limited, especially in the era of intensity-modulated RT (IMRT). Objective: To evaluate the taste function in patients with HNC receiving IMRT by investigating the association between time course and recovery of TD in both acute and late phases. Design, Setting, and Participants: From August 2017 to November 2020, patients treated at the Chang Gung Memorial Hospital with curative or postoperative IMRT for HNC were enrolled in this prospective cohort study. The data analysis was performed from March 2021 to January 2022. Exposures: IMRT with and without concurrent chemotherapy. Main Outcomes and Measures: Taste function was measured using the whole-mouth solution method for 4 tastes (salt, sweet, sour, and bitter). Subjective evaluations (National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03] and Subjective Total Taste Acuity scale) were used. Patient self-reported quality of life was evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35). Results: A total of 87 patients (78 [90%] men and 9 [10%] women; mean [range] age, 58 [31-80] years) were enrolled. Overall TD rates were 79 of 86 (91.9%), 63 of 83 (75.9%), 27 of 81 (33.3%), 5 of 56 (8.9%), and 2 of 30 (6.7%) during RT, and 1 week, 3 months, 6 months, and 1 year after RT, respectively. Positive correlation occurred between objectively measured taste loss for the 4 taste qualities and subjective perception of taste loss. Only oral cavity mean dose 4000 cGy or greater predicted TD 3 months after RT. The mean oral cavity doses to the predicted 15% (D15), 25% (D25), and 50% (D50) probabilities were 25, 38, and 60 Gy at 3 months and 57, 60, and 64 Gy at 6 months, respectively. Conclusions and Relevance: In this cohort study, most patients still experienced TD during and at 3 months after RT. Only a few patients experienced long-term TD. A high oral cavity dose was associated with TD in patients with HNC receiving IMRT. Reducing oral cavity dose may promote early recovery of taste function after IMRT.

Prognostic stratification of patients with AJCC 2018 pN1 disease in stage III oral squamous cell carcinoma.

BACKGROUND: Oral cancer with pT1-3N1 without extracapsular extension of the lymph node is classified as stage III according to the eighth edition of the AJCC staging system. Outcomes of a subgroup of patients classified as having stage III oral cancer with single nodal metastasis are observed to be various clinically. Therefore, such clinical outcomes for subgroup analyses in this cohort are necessary. METHODS: Patients with pT1-3N1 (based on the eighth edition of the AJCC staging system) oral cancer who underwent surgery between 2007 and 2016 were enrolled retrospectively for survival analyses. RESULTS: A total of 105 patients-including 28 patients with pT1N1 disease and 77 patients with pT2-3N1 disease-participated in the study. Pathological T classification was the only statistically significant prognosticator according to univariate analysis. The patients with pT1N1 disease showed better 5-year overall survival (OS), disease specific survival (DSS), and disease free survival (DFS) than those with pT2-3N1 disease (pT1N1 vs pT2-3N1, OS: 96.4% vs 72.2%, p = 0.004; DSS: 96.4% vs 77.3%, p = 0.021; DFS: 84.6% vs 62.3%, p = 0.023). Besides, there was no potential clinicopathological confounder which is significant associated with different pathological T classifications in this unique cohort. CONCLUSIONS: Patients in the pT1N1 subgroup have significantly favorable prognosis than those with pT2-3N1 disease. Down-staging and reclassifying pT1N1 subgroup patients with oral cancer may be considered in tumor staging.