Background/Objectives: We aim to investigate whether tracking pan-immune-inflammation value (PIV) dynamics during radiotherapy (RT) can inform real-time prognosis in patients with head and neck cancer (HNC). Methods: We retrospectively reviewed the medical records of patients with HNC who received RT at our institution between 2005 and 2013. Temporal changes in the PIV throughout the RT were evaluated using the Friedman test and Wilcoxon signed-rank test. The PIV dynamics were quantified using PIV ratios, defined as the PIV at three distinct time points (PIV-2, PIV-4, and PIV-6) during treatment divided by the pretreatment PIV (PIV-0). Overall survival (OS) and progression-free survival (PFS) served as the primary and secondary endpoints analyzed. Results: A total of 676 patients with HNC were enrolled, with a median follow-up of 8.1 years. The PIV demonstrated a continuously ascending trend over time, with the most dramatic increase occurring six weeks after the start of RT. Compared with patients with a low PIV ratio at six weeks (PIV-6/PIV-0), those with a high PIV ratio showed more favorable survival outcomes (five-year OS: 58.9% versus 70.8%, p = 0.002; five-year PFS: 62.0% versus 71.1%, p = 0.013). The subgroup analyses yielded consistent results. Notably, the real-time risks of death and recurrence changed in parallel with the PIV dynamics. Multivariate analysis confirmed PIV-6/PIV-0 as an independent prognostic factor for both OS and PFS. Conclusions: Monitoring longitudinal PIV dynamics may assist in forecasting the OS and PFS in patients with HNC being treated with RT, thus enabling individualized, risk-adapted treatment management.

Background Radiotherapy (RT) is a standard treatment for nasopharyngeal carcinoma (NPC), however, RT-induced immune suppression and tumor radioresistance limit durable cancer control, with approximately 20% of patients developing recurrence or metastasis after treatment. We investigated the molecular effects of RT on the immune landscape of NPC and identified a key role of the STING–ATM–MPO axis in RT-induced immune suppression, which is associated with regulatory T cell (Treg) expansion and radioresistance. Methods We analyzed leukocyte counts from 653 NPC patients before treatment and at multiple time points (week 1–2, week 3–4, and week 5–6) after RT. Single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cell (PBMC) samples from stage I NPC patients (T1N0M0) treated with RT alone. Blood samples were collected before and after 18 Gy RT (in 2 Gy fractions). A randomized six-arm syngeneic mouse tumor model and in vitro cell studies were used to investigate interactions among STING–ATM signaling, immune modulation, and tumor response. Results In NPC patients, RT suppressed cGAS–STING signaling in monocytes and dendritic cells but promoted immunosuppressive programs, including PD-1 signaling, checkpoint expression, regulatory T cell expansion, and upregulation of TGFβ1, IL-10, VEGF, PDGF, and MDSC-associated pathways. In a syngeneic mouse model, co-treatment with the STING agonist diABZI reversed these effects and improved tumor control. Bulk RNA sequencing confirmed that RT suppressed cGAS–STING and ATM signaling in both spleens and tumors. Combination treatment restored this signaling, enhanced neutrophil degranulation, and inhibited PD-1 signaling and immune checkpoints. Immunohistochemistry showed that diABZI increased ATM activation, MPO expression, and reduced Treg infiltration in spleens and tumors. ATM activation correlated positively with MPO and inversely with FOXP3 immunoreactivity, suggesting that STING–ATM–MPO activation counteracts Treg-mediated immune suppression. In vitro, diABZI activated STING–ATM signaling in PBMCs, THP-1 cells, and Jurkat T cells, while inhibiting NPC cell growth partly via CYLD upregulation. Conclusions These findings link RT-induced suppression to inhibition of cGAS–STING signaling. Activation of STING-ATM-MPO axis counteracts Treg-mediated immune suppression, supporting the therapeutic potential of STING agonists as radiosensitizers in NPC. ### Competing Interest Statement The authors have declared no competing interest.

Nasopharyngeal carcinoma (NPC) is characterized by Epstein-Barr virus (EBV) infection and severe immune cell infiltration. How tumor-derived EBV or viral products regulate macrophage polarization within NPC microenvironment remains to be explored. Here, we investigated the exosome-mediated intercellular communications between EBV+ NPC cells and tumor-associated macrophages (TAMs). We demonstrate that leukemia inhibitory factor (LIF) expression correlates with poorer metastasis/recurrence-free survival in NPC patients. Immunohistochemical analyses revealed that LIF is highly expressed by both tumor cells and macrophages. The uptake of NPC-derived exosomes by human monocyte-derived macrophages induced an immunosuppressive polarization and enhanced LIF expression, exhibiting a reduced cytotoxicity against primary cancer cells. Blocking LIF suppressed the pro-tumor functions mediated by tumor-derived exosomes, in both in vitro and in vitro zebrafish xenografts model. Furthermore, single-cell transcriptomic analysis (scRNA-seq) suggested that tumor-derived exosomes remodeled the NPC microenvironment by increasing the proportion of a pro-tumoral TAM subtype, CCL18-TAM. Intercellular analysis revealed that exosome-treated macrophages could modulate T cell cytotoxicity and promoting Treg-mediated immunosuppression. Collectively, EBV shapes the tumor microenvironment by driving macrophage toward an immunosuppressive phenotype via exosome cargos, facilitating a pro-tumoral niche and contribute to NPC progression. ### Competing Interest Statement The authors have declared no competing interest.

Supplementary Data from Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes

Purpose Nasopharyngeal carcinoma is highly metastatic but difficult to detect in its early stages. It is critical to develop a simple and highly efficient molecular diagnostic method for early detection of NPC in clinical biopsies. Methods The transcriptomic data of primary NPC cell strains were used as a discovery tool. Linear regression approach was used to define signatures distinctive between early and late stage of NPC. Expressions of candidates were validated with an independent set of biopsies (n = 39). Leave-one-out cross-validation technique was employed to estimate the prediction accuracy on stage classification. The clinical relevance of marker genes was verified using NPC bulk RNA sequencing data and IHC analysis. Results Three genes comprising CDH4, STAT4, and CYLD were found to have a significant differentiating power to separate NPC from normal nasopharyngeal samples and predicting disease malignancy. IHC analyses showed stronger CDH4, STAT4, and CYLD immunoreactivity in adjacent basal epithelium compared with that in tumor cells ( p < 0.001). EBV-encoded LMP1 was exclusively expressed in NPC tumors. Using an independent set of biopsies, we showed that a model combining CDH4, STAT4, and LMP1 had a 92.86% of diagnostic accuracy, whereas a combination of STAT4 and LMP1 had a 70.59% accuracy for predicting advanced disease. Mechanistic studies suggested that promoter methylation, loss of DNA allele, and LMP1 contributed to the suppressive expression of CDH4, CYLD, and STAT4, respectively. Conclusion A model combining CDH4 and STAT4 and LMP1 was proposed to be a feasible model for diagnosing NPC and predicting late stage of NPC.

Supplementary Figures, Tables, and Methods

BACKGROUND:The progression of nasopharyngeal carcinoma (NPC) is profoundly affected by Epstein-Barr virus (EBV) infection. However, the role of EBV in the intercommunication between NPC and surrounding stromal cells has yet to be explored.METHODS:NPC biopsies were obtained for immunohistochemical (IHC) analyses. Clinical correlations between the expression of active YAP1/FAPα and the fibrotic response and between YAP1/FAPα and the density of cytotoxic CD8a+ T lymphocytes were determined. Survival times based on IHC scores were compared between groups using Kaplan-Meier survival and log-rank tests. Independent prognostic factors for metastasis/recurrence-free survival and overall survival were identified using univariate and multivariate Cox regression models. Fibroblasts were isolated from human nasopharyngeal biopsies. Exosomes were purified from culture supernatants of EBV+-positive NPC cells. The effects of EBV product-containing exosomes on fibroblast activation, fibrotic response, tumor growth, immune response, and correlations between the expression of featured genes were investigated using gel contraction assays, ELISAs, EdU incorporation assays, real-time impedance assays, RNA sequencing, immunostaining, 3D cancer spheroid coculture systems, and an NPC xenograft model.RESULTS:NPC patients who developed metastasis had significantly higher levels of active YAP1 and FAPα in their tumor stroma, which was further correlated with tumor fibrosis and poorer metastasis-free survival. Exosomes released from EBV+-NPC cells contained abundant FAPα protein and EBV-encoded latent membrane protein 1. Viral product-containing exosomes markedly enhanced the fibrotic response and tumor growth in a mouse xenograft model. IHC analyses of human NPC and NPC xenografts revealed positive correlations between levels of active YAP1 and FAPα, YAP1 and the fibrotic response, and FAPα and the fibrotic response. Mechanistic studies showed that treatment of fibroblasts with viral product-containing exosomes promoted the characteristics of cancer-associated fibroblasts by stimulating YAP1 signaling and the production of the immunosuppressive cytokines IL8, CCL2, and IL6. Inhibition of YAP1 activation markedly reversed these exosome-mediated protumoral effects, resulting in reduced contractility, inactivation of YAP1 signaling, and decreased production of immunosuppressive cytokines in fibroblasts. Furthermore, fibroblasts stimulated with these viral product-containing exosomes promoted NPC resistance to T cell-mediated cytotoxicity within tumor spheroids. In NPC tissues, a significant negative correlation was found between YAP1/FAPα and the density of CD8a+ T lymphocytes with a granzyme B signature.CONCLUSION:EBV orchestrates interactions with the host and surrounding stroma by stimulating the functions of YAP1 and FAPα in fibroblasts through exosome cargos to create a more immunosuppressive, proinvasive microenvironment.

Epstein-Barr virus (EBV) infection is intimately associated with type III nasopharyngeal carcinoma (NPC). Most NPCs respond well to chemoradiation. Nevertheless, approximately 20% of patients experience recurrence and distant metastasis. Tumor desmoplastic responses and high densities of cancer-associated fibroblasts (CAFs) within tumors have been correlated with poorer prognosis. In this study, we demonstrate that EBV activates fibroblasts via exosomes to remodel a pro-tumoral microenvironment. Exosomes derived from NPC cells contained a high level of fibroblast activation protein alpha (FAPα) and EBV-encoded latent membrane protein 1 (LMP1). Treating primary fibroblasts with these exosomes induced functional changes resembling CAFs. Transcriptomic analysis on exosome-treated fibroblasts revealed genes involved in fibrosis-associated pathways were enriched. Noticeably, treating with EBV products-containing exosomes in fibroblasts enhanced the production of several immune-suppressive cytokines, including IL6, IL8, and MCP-1. Moreover, stimulation with these exosomes enhanced activation of YAP1 signaling, a key pathway linking to fibrosis. The in vivo mouse xenografted NPC studies showed that EBV products-containing exosomes markedly enhanced the severity of tissue fibrosis and tumor growth. IHC analysis on mouse NPC xenografts and human NPC biopsies showed a positive correlation between levels of nuclear YAP1 and FAPα, which were further correlated with an enhanced fibrotic response within tumors. Pharmaceutical intervention with YAP1 inhibitors blocked the exosome-mediated effects on fibroblasts. Collectively, our data suggest that EBV products-containing exosome is a causal factor in CAF formation, which constitutes a pro-tumoral microenvironment to benefit the survival of both tumor and virus itself. Citation Format: Po-Ju Lee, Yun-Hua Sui, Chen-Han Huang, Tzu-Tung Liu, Ngan-Ming Tsang, Shu-Chen Liu. EBV-products containing exosomes remodel NPC tumor microenvironment by activating fibroblasts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3192.

Background Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. Material and methods This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016–2017 in Taiwan, aged 20–64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. Results Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80–3.63, P < .001) for frail and fit patients, respectively. Conclusions This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Background and purpose: We sought to investigate whether dynamic changes in lymphocyte-tomonocyte ratio (LMR) occurring during the course of radiotherapy (RT) may have prognostic value in patients with head and neck cancer (HNC). Materials and methods: We retrospectively reviewed the clinical records of patients with HNC who underwent RT at our center between 2005 and 2013. Generalized estimating equations were used to longitudinally assess changes in LMR through the course of RT. Delta-LMR was calculated as the difference between LMR measured during treatment and baseline LMR values. Freedom from metastasis (FFM) and overall survival (OS) served as the main outcome measures. Results: A total of 1431 patients with HNC were enrolled. After a median follow-up of 9 years, 636 (44.4%) patients died and 240 (16.8%) had distant metastases. Compared with patients with low delta-LMR at two weeks, those with high delta-LMR experienced less favorable outcomes (five-year OS: 73% versus 59%, respectively, p < 0.001; five-year FFM: 87% versus 80%, respectively, p = 0.015). Similar findings were observed for delta-LMR measured at four weeks (five-year OS: 72% versus 60%, p < 0.001; five-year FFM: 86% versus 79%, respectively, p = 0.002) and six weeks (five-year OS: 72% versus 57%, p < 0.001; five-year FFM: 87% versus 79%, respectively, p = 0.002). Multivariate analysis identified delta-LMR as an independent prognostic factor for both FFM and OS. Conclusion: Delta-LMR is a simple and inexpensive biomarker that may be clinically useful for predicting FFM and OS in patients with HNC treated with RT. (C) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology

Abstract Background We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). Methods We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. Results The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656–0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478–0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high‐risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)—with a borderline significance being evident for DC in patients with T4 disease (p = 0.058). Conclusions A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance.

OBJECTIVE:To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS:We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS:Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (β-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal β-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased β-hCG levels, those with β-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS:Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with β-hCG levels <5 mIU/mL.

Abstract The most frequent location of metastatic EBV+ nasopharyngeal carcinoma (NPC) is the bone marrow, an adipocyte-dominant region. Several EBV-associated lymphoepithelioma-like carcinoma (LELC) types also grow in the anatomical vicinity of fat tissues. Here we show that in an adipose tissue-rich tumor setting, EBV targets adipocytes and remodels the tumor microenvironment. Positive immunoreactivity for EBV-encoded early antigen D was detected in adipose tissue near tumor beds of bone marrow metastatic NPC. EBV was capable of infecting primary human adipocytes in vitro, triggering expression of multiple EBV-encoded mRNA and proteins. In infected adipocytes, lipolysis was stimulated through enhanced expression of lipases and the AMPK metabolic pathway. The EBV-mediated imbalance in energy homeostasis was further confirmed by increased release of free fatty acids, glycerol, and expression of proinflammatory adipokines. Clinically, enhanced serum levels of free fatty acids in patients with NPC correlated with poorer recurrence-free survival. EBV-induced delipidation stimulated dedifferentiation of adipocytes into fibroblast-like cells expressing higher levels of S100A4, a marker protein of cancer-associated fibroblasts (CAF). IHC analyses of bone marrow metastatic NPC and salivary LELC revealed similar structural changes of dedifferentiated adipocytes located at the boundaries of EBV+ tumors. S100A4 expression in adipose tissues near tumor beds correlated with fibrotic response, implying that CAFs in the tumor microenvironment are partially derived from EBV-induced dedifferentiated adipocytes. Our data suggest that adipose tissue serves as an EBV reservoir, where EBV orchestrates the interactions between adipose tissues and tumor cells by rearranging metabolic pathways to benefit virus persistence and to promote a protumorigenic microenvironment. Significance: This study suggests that Epstein–Barr virus hijacks adipocyte lipid metabolism to create a tumor-promoting microenvironment from which reactivation and relapse of infection could potentially occur.

BACKGROUND/AIM:The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT).PATIENTS AND METHODS:Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival.RESULTS:A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046].CONCLUSION:Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.

Background/Aim: This study was designed to clarify the value of routine alpha-fetoprotein (AFP) testing for patients with gastric cancer (GC). Patients and Methods: A total of 905 patients with newly diagnosed GC and available pretreatment carcinoembryonic antigen (CEA), cancer-related antigen 19-9 (CA19-9), and AFP data from 2010 to 2016 were collected for comparison of tumor stage and survival. Results: In total, 139 patients (15.4%), 155 patients (17.1%), and 27 patients (3.0%) had elevated CEA, CA19-9, and AFP levels, respectively. The c-index values of elevated AFP levels in predicting stage IV disease and the 1-year mortality rate were 0.564 (95%CI=0.520-0.608) and 0.594 (95%CI=0.553-0.635), respectively, which were significantly lower than those of CEA (0.673 and 0.665) and CA19-9 (0.619 and 0.618). Conclusion: Elevated AFP is rare in patients with newly diagnosed GC. Routine AFP sampling would not provide a higher survival prediction in GC patients than CEA or CA19-9.

Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9–6.3% and 14.5–18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801–0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools. MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

Background: Comprehensive Geriatric Assessment (CGA) is the gold standard for detecting frailty in elderly patients with cancer. Since CGA is time- and resource-consuming, many alternative frailty screening tools have been developed; however, it remains unknown whether these tools are suitable for older and adult patients with cancer. Therefore, we used the data collected for a large longitudinal study to compare the diagnostic performances of two frailty screening tools (Geriatric 8 [G8] and Flemish version of the Triage Risk Screening Tool [fTRST]) to identify frailty risk profile among patients with cancer. Methods: Patients aged >= 20 years with newly diagnosed cancer were enrolled. Frailty screening with G8, fTRST, and CGA were performed before anti-cancer treatment. Diagnostic characteristics obtained using G8 and fTRST were analyzed by C-index, and the validity of G8 and fTRST was also determined. Results: 40.9% of the 755 patients with cancer displayed frailty on CGA. Both G8 and fTRST showed high sensitivity (80.6-88.4%) and negative predictive value (81.0-81.2%). The C-index of G8 was higher than that of fTRST (0.77 vs 0.71, p = .01). Moreover, the best G8 and fTRST cut-off points were <= 13 and >= 2, respectively. The validities of G8 and fTRST were also confirmed; however, frailty age differences were not observed in our study. Conclusion: Frailty is a common problem for patients with cancer, and routine frailty screening is essential for both older and adult patients. G8 and fTRST are simple and useful frailty screening tools, while G8 is more suitable than fTRST for Taiwanese patients with cancer.

Purpose: This study aimed to identify vulnerable patients with head and neck cancer undergoing concurrent chemoradiation therapy (CCRT) who are susceptible to higher treatment-related adverse effects and have poorer treatment tolerance. This study also aimed to determine whether comprehensive geriatric assessment, developed in the geriatric population, can predict vulnerability to treatment-related adverse events and survival even in nongeriatric patients with head and neck cancer, as well as the prevalence of vulnerability and its effect on toxicities and survival among these patients. Methods and Materials: This prospective cohort study examined 461 patients with primary head and neck cancer who underwent definitive CCRT during 2016 to 2017 at 3 medical centers across Taiwan. Vulnerability is defined as susceptibility to cancerand treatment-related adverse events that result in poor treatment tolerance and unexpected emergent medical needs, such as hospitalization and emergency room visits. Vulnerability was assessed as impairment with >= 2 dimensions on comprehensive geriatric assessment, 7 days before CCRT. The association of vulnerability with treatmentrelated adverse events and survival was analyzed. Results: The prevalence of vulnerability was 22.2%, 27.3%, 30.2%, and 27.9% among patients aged 20 to 34, 35 to 49, 50 to 64, and >65 years, respectively. Survival was poorer in vulnerable patients than in nonvulnerable patients (hazard ratio, 1.97; 95% confidence interval, 1.26-3.07; P = .003). Vulnerable patients showed a higher tendency toward CCRT incompletion (19.5% vs 6.1%, P < .001), hospitalization (34.6% vs 23.5%, P = .020), need for tubal feeding (29.3% vs 11.8%, P < .001), and longer length of hospital stay (8.1 days vs 4.0 days, P = .004) than nonvulnerable patients. Hematologic and nonhematologic toxicities were more severe in vulnerable patients than in nonvulnerable patients. Conclusions: Vulnerability, which is an urgent concern when it presents among patients with head and neck cancer, was independently associated with poorer survival and severe treatment-related complications. Vulnerability assessment should be routinely evaluated in all patients with primary head and neck cancer who are undergoing definitive CCRT, not only in such patients who are geriatric. (C) 2020 Elsevier Inc. All rights reserved.

Background and purpose: To develop and validate a magnetic resonance imaging (MRI)-derived radiomic signature (RS) for the prediction of 1-year locoregional failure (LRF) in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who received organ preservation therapy (OPT) Material and methods: A total of 800 MRI-based features of pretreatment tumors were obtained from 116 patients with HPSCC who received OPT from two independent cohorts. The least absolute shrinkage and selection operator regression model were used to select the features used to develop the RS. Harrell's C index and corrected C-index were used to evaluate the discriminative ability of RS. The Youden index was used to select the optimal cut-point for risk category. Results: The RS yielded 1000 times bootstrapping corrected C-index of 0.8036 and 0.78235 in the experimental (n = 82) and validation cohorts (n = 34), respectively. With respect to the subgroup of patients with stage III/IV and cT4 disease, the RS also showed good predictive performance with corrected C indices of 0.760 and 0.754, respectively. The dichotomized risk category using an RS of 0.0326 as the cut-off value yielded a 1-year LRF predictive accuracy of 79.27%, 79.41%, 76.74%, and 71.15% in the experimental, validation, stage III/IV, and cT4a cohorts, respectively. The low-risk group was associated with a significantly better progression-free laryngectomy-free and overall survival outcome in two independent institutions, stage III/IV, and cT4a cohorts. Conclusion: The RS-based model provides a novel and convenient approach for the prediction of the 1 year LRF and survival outcome in patients with HPSCC who received OPT. (c) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

The aim of this study is to develop a computer-aided diagnosis method to help classify medical images of neck lymph nodes in head and neck cancer patients. According to the current practice guidelines, the classification of lymph node status is critical for patient stratification before treatment. Take extra-nodal extension (ENE) of metastatic neck lymph nodes, the status of ENE has been considered a single factor affecting the decision of whether systemic treatment with toxicity should be given to patients with otherwise non-advanced cancer status. Medical imaging prior to surgery serves as tools for clinical staging and determining the extent of neck lymph node dissection during the tumor resection surgery. The information contained in these images may also help determine the status of ENE and thus stratify patients for more precise treatment. In the current practice, there has been not a reliable computer-aided tool for this task. In this study, we used open-source software to investigate radiomic features that help distinguish malignant from benign and ENE from non-ENE lymph nodes. We have identified 89 features that can differentiate malignant from benign and 4 features that can differentiate ENE from non-ENE lymph nodes. Furthermore, we fed the significant features to a multilayer perceptron neural network to predict malignancy and ENE of lymph nodes and achieved 84% and 77% of accuracy in each task, respectively.