Systemically Administered D-allose Inhibits the Tumor Energy Pathway and Exerts Synergistic Effects With Radiation.

BACKGROUND/AIM: The present study investigated the anticancer effects of intraperitoneally administered D-allose in in vivo models of head and neck cancer cell lines. MATERIALS AND METHODS: To assess the direct effects of D-allose, its dynamics in blood and tumor tissues were examined. RESULTS: D-allose was detected in blood and tumor tissues 10 min after its intraperitoneal administration and then gradually decreased. In vivo experiments revealed that radiation plus D-allose was more effective than either treatment alone. Thioredoxin-interacting protein (TXNIP) mRNA over-expression was detected after the addition of D-allose in in vitro and in vivo experiments. D-allose inhibited cell growth, which was associated with decreases in glycolysis and intracellular ATP levels and the prolonged activation of AMPK. The phosphorylation of p38-MAPK was also observed early after the administration of D-allose and was followed by the activation of AMPK and up-regulated expression of TXNIP in both in vitro and in vivo experiments. CONCLUSION: Systemically administered D-allose appears to exert antitumor effects. Further studies are needed to clarify the appropriate dosage and timing of the administration of D-allose and its combination with other metabolic agents.

Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

The Utility of Glasgow Prognostic Score and Palliative Prognostic Index in Patients With Head and Neck Squamous Cell Carcinoma Under Palliative Care.

OBJECTIVES: Palliative care patients with head and neck squamous cell carcinoma (HNSCC) often experience dysphagia and airway trouble; thus, each patient requires a specific palliative care plan based on their prognostication. However, no established specific prognostic tool performed on the day of starting end-of-life care is available for such patients. We assessed the accuracy of Glasgow prognostic score (GPS) and palliative prognostic index (PPI) and their combination to establish a specified prognostic tool for patients with HNSCC in end-of-life setting. METHODS: A retrospective clinical chart review was undertaken on patients with HNSCC in end-of life setting who were decided in Kagawa University Hospital and National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. The patients were divided into 2 categories according to GPS (0-1 and 2) and PPI (groups A-B and C). These were combined into 4 categories (PPI group A-B and GPS score 0-1: good; PPI group A-B and GPS score 2: intermediate; PPI group C and GPS score 2: poor; and PPI group C and GPS score 0-1: others). The survival curves were compared for the former 3 categories. RESULTS: The median survival of the scores 0-1 and 2 on GPS were 114 (72-148) and 39 (25-52) days, respectively (P < .01). These of groups A-B and C on PPI were 79 (64-99) and 16 (9-29) days, respectively (P < .01). The median survival of the good, intermediate, and poor categories was 127 (73-149), 64 (44-80), and 15 (9-27) days, respectively (P < .01 among all categories). CONCLUSIONS: In this study, the survival of terminally ill patients with HNSCC can be predicted by the GPS, PPI, and their combination with sufficient probability.

Influence of volumetric 4'-[methyl-11C]-thiothymidine PET/CT parameters for prediction of the clinical outcome of head and neck cancer patients.

OBJECTIVE: This prospective study compared the value of pretreatment 4'-[methyl-11C]-thiothymidine (11C-4DST) volumetric parameters and those of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) in predicting the clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Fifty patients with HNSCC underwent 11C-4DST PET/CT and 18F-FDG PET/CT prior to anticancer therapy. 18F-FDG metabolic tumor volume (18F-FDG MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET, and 11C-4DST MTV and total lesion proliferation (TLP) were calculated from 11C-4DST PET. All parameters were measured for the primary lesion and metastatic lymph nodes. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: Receiver-operating characteristic analysis revealed that MTV, TLG, and TLP acquired from the primary lesion and metastatic lymph nodes were good parameters for predicting disease relapse and death. The area under the curves (AUCs) ranged from 0.63 to 0.71 for 18F-FDG PET/CT parameters. The AUCs of 11C-4DST PET/CT parameters were larger than those of 18F-FDG (range 0.72-0.81). Univariate analysis revealed that individuals with tumors showing a high value for any PET/CT parameter were at a significantly increased risk of relapse. Upon multivariate analysis, 18F-FDG MTV, 11C-4DST MTV and 11C-4DST TLP were significant independent factors for relapse-free survival (P = 0.04, P = 0.0001 and P = 0.0005, respectively). CONCLUSION: Pretreatment 11C-4DST PET/CT volume-based parameters can provide important prognostic information about patients with HNSCC.