Comparison of healthcare utilization and life-sustaining interventions between patients with glioblastoma receiving palliative care or not: A population-based study.

BACKGROUND: Palliative care has historically been under-utilized in patients with glioblastoma. Furthermore, literature on the utilization of healthcare and life-sustaining interventions during the late-stage of glioblastoma has been limited. AIM: To identify and compare healthcare utilization and life-sustaining interventions between patients with glioblastoma who received palliative care and who did not based on patients identified retrospectively from Taiwan Cancer Registry between January 2007 and December 2017. DESIGN: In this study, palliative care was defined on the basis of claims submitted to the National Health Insurance, which has a specific code for it. Variables included demographic characteristics, the utilization of healthcare services, and invasive life-sustaining interventions. SETTING/PARTICIPANTS: Of the 1994 patients with glioblastoma identified, 1784 fulfilled the inclusion criteria, 613 (34%) of whom received palliative care. RESULTS: The survival of patients with glioblastoma under palliative care was significantly longer than that of those without palliative care. Those without palliative care had significantly more frequent intensive care unit admissions and a longer cumulative length of intensive care unit stay. Regarding cardiopulmonary or respiratory treatments, patients without palliative care had significantly more invasive interventions than those with palliative care. Patients receiving palliative care had significantly lower odds than those without life-sustaining interventions. CONCLUSIONS: Our retrospective analysis reveals that glioblastoma patients without palliative care had greater odds of receiving life-sustaining treatments within 1 year before their death, although no gains in survival as compared to those that received palliative care. These findings highlight the urgent need for palliative care in caring for patients with glioblastoma.

Treatment outcomes of primary surgery versus chemoradiotherapy for T4 oropharyngeal cancers.

Concurrent chemoradiotherapy (CCRT) has been the standard of care for locally advanced diseases regardless of human papillomavirus infection status. Other treatment options include surgery followed by adjuvant therapy and induction chemotherapy followed by CCRT or radiotherapy. However, for locally advanced T4 laryngeal or hypopharyngeal diseases, surgery is preferred over CCRT. Given the improvement in the functional outcomes of surgery, examining the oncologic outcomes in OPSCC patients is critical. This study aimed to determine whether differences in overall survival (OS) exist between surgery and CCRT. Oropharyngeal cancer patients included in the cancer registry of our hospital from January 2014 to December 2018 were retrospectively analyzed. Patients with T4 disease who underwent curative treatment were identified. In this study, the primary and secondary outcomes were OS and disease-free survival (DFS), respectively. Potential confounding factors were also evaluated. Details regarding recurrence pattern were listed. From 2014 to 2018, 74 newly diagnosed oropharyngeal cancer patients were identified from our cancer registry database, 60 of whom satisfied our inclusion criteria. Our findings showed an OS of 25.5 months and DFS of 17.5 months. No significant difference in both of OS and DFS were observed between the surgery and CCRT cohorts. Sex, stage, second primary cancer, IC, and primary treatment were not correlated with DFS. Male sex was the only significant factor identified, with an HR of 0.2 for OS (95% confidence interval, 0.06-0.71). No significant difference in both OS and DFS were observed between the CCRT and surgery cohorts. CCRT remains the standard of care for locally advanced disease.

Cordycepin enhances radiosensitivity to induce apoptosis through cell cycle arrest, caspase pathway and ER stress in MA-10 mouse Leydig tumor cells.

Radiotherapy is a localized treatment commonly used in various types of cancer. However, major limitation of radiotherapy is the development of resistance of tumor cells to radiosensitivity. Cordycepin, a predominant functional component of the Cordyceps sinensis, is considered to use in treating tumor cells. In the present study, we investigated the anticancer effect of the combination of radiation and cordycepin in the treatment of Leydig tumor cells. Results showed that the combination treatment has a synergistic effect significantly suppress cell viability and enhance the radiosensitivity in MA-10 mouse Leydig tumor cells. The combination treatment induced MA-10 cell apoptosis through increasing levels of cleaved caspase-3/-8/-9, poly ADP-ribose polymerase (PARP), and cytochrome c and decreasing levels of B-cell lymphoma 2 (Bcl-2). In addition, prolonged sub-G1 and G2/M arrest accompany with cell cycle-related protein regulation was observed in cells that received the combination treatment. The endoplasmic reticulum (ER) stress-related protein expressions were regulated after MA-10 cells treating with a combination of 100 µM cordycepin and 4 Gy radiation. Furthermore, the combination treatment also decreased the Leydig tumor mass by increasing cell apoptosis in tumor-bearing mice. In conclusion, cordycepin enhances radiosensitivity to induce mouse Leydig tumor cells toward apoptosis in vitro and in vivo. This study will provide a scientific basis for the development of therapeutic regimen of testicular cancer.

Mechanisms of Nanotoxicology and the Important Role of Alternative Testing Strategies.

Recently, rapid advances in nanotechnology have provided a lot of opportunities for the mass production of engineered nanomaterials of various types of chemicals, including metals and nonmetals, promoting the development of a new generation of industrial and commercial products and the field of nanomedicine [...].

Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases: Results of a retrospective analysis.

ABSTRACT: Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.

Retrospective analysis of adjuvant radiotherapy in oral cavity or oropharyngeal cancer: Feasibility of omitting lower-neck irradiation.

OBJECTIVES: Adjuvant radiotherapy is the standard of care in locally advanced head and neck cancers. The radiation field is correlated with the surgical field in the adjuvant radiotherapy setting; therefore, tailoring the irradiation field is reasonable. MATERIALS AND METHODS: We retrospectively analyzed patients with oral cavity and oropharyngeal cancers included in the cancer registry between 2015 and 2019 in the study hospital. Patients who underwent whole-neck irradiation (WNI) were compared with those who underwent lower-neck-sparing (LNS) irradiation. RESULTS: A total of 167 patients with oral cavity and oropharyngeal cancers were included in the study. Cancer recurrence was recorded in 33% of the patients. The rate of recurrence of oral cavity and oropharyngeal cancer at neck level IV was 8%. The 2-year incidence of level IV recurrence was lower in the WNI group than in the LNS group (2% vs. 10%; p = 0.04). The 2-year disease-free survival rates were 75% and 63% in the WNI and LNS groups, respectively (p = 0.08). CONCLUSION: The rate of level IV recurrence was higher in the LNS group than in the WNI group. Trends of improvement in disease-free survival with lower-neck irradiation suggested that it is premature to consider LNS irradiation as daily practice in patients with oral cavity and oropharyngeal cancer.

Epidemiologic Features, Survival, and Prognostic Factors Among Patients With Different Histologic Variants of Glioblastoma: Analysis of a Nationwide Database.

Background: Glioblastoma (GBM) is the most common primary intracranial malignancy. Previous studies found incidence of GBM varies substantially by age, sex, race and ethnicity, and survival also varies by country, ethnicity, and treatment. Gliosarcoma (GSM) and giant cell glioblastoma (GC-GBM) are different histologic variants of GBM with distinct clinico-pathologic entities. We conducted a study to compare epidemiology, survival, and prognostic factors among the three. Methods: We identified GBM patients diagnosed between 2000 and 2016 using the Taiwan Cancer Registry and followed them using the death registry. Survival was compared among conventional GBM and two histologic variants. The potential confounding factors evaluated in this study included registered year, age, sex, and treatment modality (resection, radiotherapy, and chemotherapy). Results: We enrolled 3,895 patients, including 3,732 (95.8%) with conventional GBM, 102 (2.6%) with GSM, and 61 (1.6%) with GC-GBM. GC-GBM patients had younger mean age at diagnosis (49.5 years) than conventional GBM patients (58.7 years) and GSM patients (61.3 years) (p < 0.01). The three groups had similar sex distributions (p = 0.29). GC-GBM had a longer median survival [18.5, 95% confidence interval (CI): 15.8-25.3 months] than conventional GBM (12.5, 95%CI: 12.0-13.0 months) and GSM (12.8, 95%CI: 9.2-16.2 months), and the differences in overall survival did not attain statistical significance (p = 0.08, log-rank test). In univariate analysis, GC-GBM had better survival than conventional GBM, but the hazard ratio (0.91) did not reach statistical significance (95%CI: 0.69-1.20) in the multivariate analysis. Young ages (≤ 40 years), female sex, resection, radiotherapy, and chemotherapy were factors associated with better survival in overall GBMs. In subtype analyses, these factors remained statistically significant for conventional GBM, as well as radiotherapy for GSM. Conclusion: Our analysis found conventional GBM and its variants shared similar poor survival. Factors with age ≤ 40 years, female sex, resection, radiotherapy, and chemotherapy were associated with better prognosis in conventional GBM patients.

Clinical significance of olfactory dysfunction in patients of COVID-19.

BACKGROUND: Currently, as the coronavirus disease (COVID-19) has become a pandemic, rapidly obtaining accurate information of patient symptoms and their progression is crucial and vital. Although the early studies in China have illustrated that the representative symptoms of COVID-19 include (dry) cough, fever, headache, fatigue, gastrointestinal discomfort, dyspnea, and muscle pain, there is increasing evidence to suggest that olfactory and taste disorder are related to the COVID-19 pandemic. Therefore, we conduct this study to review the present literature about the correlation between anosmia or dysgeusia and COVID-19. METHODS: A comprehensive literature search in 2020 of the electronic journal databases, mainly PubMed or Web of Science, was performed using the keywords COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with hyposmia, anosmia, dysgeusia, olfactory disorder, or olfactory dysfunction. The country, study period, case number, inpatient or outpatient medical visit, evaluation method (subjective complaints of dysfunction or objective evaluation), and occurrence rate of olfactory or gustatory function were reviewed. RESULTS: Many studies reported that the recoverable olfactory or gustatory dysfunction may play an important role as the early clinical symptom of COVID-19. It is associated with better prognosis, although further investigation and validation should be carried out. CONCLUSION: Studies have shown that smell and taste disturbances may represent an early symptom of COVID-19 and healthcare professionals must be very vigilant when managing patients with these symptoms. In the pandemic era, this implies testing for COVID-19 by healthcare workers with full personal protective equipment.

Chloroquine and Hydroxychloroquine: Efficacy in the Treatment of the COVID-19.

Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.

Calibration of the EBT3 Gafchromic Film Using HNN Deep Learning.

To achieve a dose distribution conformal to the target volume while sparing normal tissues, intensity modulation with steep dose gradient is used for treatment planning. To successfully deliver such treatment, high spatial and dosimetric accuracy are crucial and need to be verified. With high 2D dosimetry resolution and a self-development property, the Ashland Inc. product EBT3 Gafchromic film is a widely used quality assurance tool designed especially for this. However, the film should be recalibrated each quarter due to the "aging effect," and calibration uncertainties always exist between individual films even in the same lot. Recently, artificial neural networks (ANN) are applied to many fields. If a physicist can collect the calibration data, it could be accumulated to be a substantial ANN data input used for film calibration. We therefore use the Keras functional Application Program Interface to build a hierarchical neural network (HNN), with the inputs of net optical densities, pixel values, and inverse transmittances to reveal the delivered dose and train the neural network with deep learning. For comparison, the film dose calculated using red-channel net optical density with power function fitting was performed and taken as a conventional method. The results show that the percentage error of the film dose using the HNN method is less than 4% for the aging effect verification test and less than 4.5% for the intralot variation test; in contrast, the conventional method could yield errors higher than 10% and 7%, respectively. This HNN method to calibrate the EBT film could be further improved by adding training data or adjusting the HNN structure. The model could help physicists spend less calibration time and reduce film usage.

Relationship between Semi-Quantitative Parameters of Thallium-201 Myocardial Perfusion Imaging and Coronary Artery Disease.

This study aimed to investigate the diagnostic performance of semi-quantitative parameters of thallium-201 myocardial perfusion imaging (MPI) for coronary artery disease (CAD). From January to December 2017, patients were enrolled who had undergone Tl-201 MPI and received cardiac catheterization for coronary artery disease within three months of MPI. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values of semi-quantitative parameters. A comparison of the sensitivity and specificity of these parameters based on different subgroupings was further performed. A total of 130 patients were enrolled for further analysis. Among the collected parameters, the stress total perfusion deficit (sTPD) had the highest value of the area under curve (0.813) under the optimal cutoff value of 3.5%, with a sensitivity and specificity of 73.5% and 74.5%, respectively (p = 0.0000), for the diagnosis of CAD. With further subgrouping analysis based on history of diabetes or dyslipidemia, the sensitivity and specificity showed similar results. Based on the currently collected data and image acquisition conditions, the sTPD parameter has a clinical role for the diagnosis of CAD with a cutoff value of 3.5%.

The Recent Progress in Nanotoxicology and Nanosafety from the Point of View of Both Toxicology and Ecotoxicology.

This editorial aims to summarize the 14 scientific papers contributed to the Special Issue "Nanotoxicology and nanosafety 2.0 from the point of view of both toxicology and ecotoxicology".

Survival of glioblastoma treated with a moderately escalated radiation dose-Results of a retrospective analysis.

Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors and typically tends to recur locally just adjacent to the original tumor site following surgical resection and adjuvant radiotherapy. We conducted a study to evaluate the survival outcomes between a standard dose (≤ 60 Gy) and moderate radiation dose escalation (>60 Gy), and to identify prognostic factors for GBM. We retrospectively reviewed the medical records of primary GBM patients diagnosed between 2005 and 2016 in two referral hospitals in Taiwan. They were identified from the cancer registry database and followed up from the date of diagnosis to October 2018. The progression-free survival (PFS) and overall survival (OS) were compared between the two dose groups, and independent factors for survival were analyzed through Cox proportional hazard model. We also affirmed the results using Cox regression with least absolute shrinkage and selection operator (LASSO) approach. From our cancer registry database, 142 GBM patients were identified, and 84 of them fit the inclusion criteria. Of the 84 patients, 52 (62%) were males. The radiation dose ranged from 50.0 Gy to 66.6 Gy, but their treatment volumes were similar to the others. Fifteen (18%) patients received an escalated dose boost >60.0 Gy. The escalated group had a longer median PFS (15.4 vs. 7.9 months, p = 0.01 for log-rank test), and a longer median OS was also longer in the escalation group (33.8 vs. 12.5 months, p <0.001) than the reference group. Following a multivariate analysis, the escalated dose was identified as a significant predictor for good prognosis (PFS: hazard ratio [HR] = 0.48, 95% confidence interval [95%CI]: 0.23-0.98; OS: HR = 0.40, 95%CI: 0.21-0.78). Using the LASSO approach, we found age > 70 (HR = 1.55), diagnosis after 2010 (HR = 1.42), and a larger radiation volume (≥ 250ml; HR = 0.81) were predictors of PFS. The escalated dose (HR = 0.47) and a larger radiation volume (HR = 0.76) were identified as predictors for better OS. Following detailed statistical analysis, a moderate radiation dose escalation (> 60 Gy) was found as an independent factor affecting OS in GBM patients. In conclusion, a moderate radiation dose escalation (> 60 Gy) was an independent predictor for longer OS in GBM patients. However, prospective studies including more patients with more information, such as molecular markers and completeness of resection, are needed to confirm our findings.

Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma.

Purpose: We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. Results: The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. Conclusion: Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.

Clinical implications of multiple glioblastomas: An analysis of prognostic factors and survival to distinguish from their single counterparts.

PURPOSE: Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors. GBMs with synchronous multiple foci (multiple GBMs) is rarely diagnosed in the clinical scenario. This study aims to compare the clinical characteristics between multiple and single GBMs and to identify factors associated with the survival of GBM and evaluate their effects. METHODS: We retrospectively reviewed the medical records of patients with primary GBM in a referral medical center in Taiwan who were diagnosed between 2005 and 2016. They were identified from the cancer registry database of the center and followed from the date of diagnosis to october 2018. The primary endpoint of this study was overall survival (OS), and the independent factors for survival were identified through Cox regressions. RESULTS: A total of 48 patients were identified, of whom 44 GBM (92%) and 4 gliosarcoma (GSM) (8%). Preoperative images showed five (10%) patients had multiple brain lesions. GSM showed a high ratio of multiple lesions (50%) than patients with GBM (5%) (p = 0.05). Those with multiple lesions had significantly worse median OS of 8.2 months compared to patients with a single lesion (16 months, p = 0.03). We found that multiple GBMs was a predictor of worse survival (hazard ratio [HR] = 3.57, 95% confidence interval [95%CI]: 1.26-10.13) after adjusting for other significant predictor of radiotherapy (HR = 0.47, 95%CI: 0.23-0.96). CONCLUSION: Patients with multiple GBMs had worse survival compared to those with single GBM. GBM patients without post-operative radiotherapy were also a predictor of worse survival.

A New Histone Deacetylase Inhibitor Enhances Radiation Sensitivity through the Induction of Misfolded Protein Aggregation and Autophagy in Triple-Negative Breast Cancer.

Radiation therapy (RT) is one of the main treatments for triple-negative breast cancer (TNBC). However, many patients experience RT failure due to the metastatic potential of RT and the radiation resistance of several cancers. Histone deacetylase inhibitors (HDACis) can serve as radiosensitizers. In this study, we investigated whether a novel HDACi, TMU-35435, could reinforce radiosensitivity through the induction of misfolded protein aggregation and autophagy in TNBC. Significantly enhanced toxicity was found for the combination treatment compared with TMU-35435 or irradiation (IR) treatment alone in TNBC cells. The combination treatment induced misfolded protein aggregation and TMU-35435 inhibited the interaction of HDAC6 with dynein. Furthermore, the combined treatment induced endoplasmic reticulum (ER) stress but did not trigger apoptosis. In addition, the combination treatment caused autophagic cell death. Tumor growth in the mouse of model orthotopic breast cancer was suppressed by the combination treatment through the induction of ER stress and autophagy. These findings support the future evaluation of the novel HDACi TMU-35435, as a potent radiosensitizer in TNBC.

Calibration of Gafchromic EBT Film Using the Microtek ScanMaker 9800XL Plus Flatbed Scanner with a Modified One Red-Channel after Three-Channel Method.

PURPOSE: Using the Microtek ScanMaker 9800XL Plus (9800XL+) flatbed scanner, a method is presented to accurately calibrate EBT film, which cannot be calibrated simply using a general three-channel method because of the nonhomogeneous scanning. MATERIALS AND METHODS: Through the percentage-depth-dose method, 6-MV photon beams with two different monitor units were delivered to eight EBT2 films, each of which was tightly sandwiched in a 30-cm cubic polystyrene phantom and positioned parallel to the central axis of the beam. Before and after irradiation, all films were scanned using the Microtek 9800XL+ scanner and the pixel values (PVs) were measured along the central axis of the beam on the film and fitted to the corresponding depth doses. Before calibration, the irradiated film image was first modified using a template matrix, which was generated using the prescanned background images. Then, a modified one red-channel after three-channel method was used to calibrate the film. RESULTS: Without a template matrix, the three-channel method cannot be used because the PVs do not correspond to a rational fitting form. Using the proposed method, the difference between the fitted dose and the delivered dose is <2%. The green channel, and not the red, is found to have the largest dynamic range. CONCLUSION: The proposed technique allows the use of the three-channel method to calibrate film using a Microtek 9800XL+ scanner.

Cordycepin Enhances Radiosensitivity in Oral Squamous Carcinoma Cells by Inducing Autophagy and Apoptosis Through Cell Cycle Arrest.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and accounts for over 90% of malignant neoplasms of the oral cavity, with a 5-year survival rate of less than 50%. The long-term survival rate of OSCC patients has not markedly improved in recent decades due to its heterogeneous etiology and treatment outcomes. We investigated the anticancer effect of the combination of irradiation (IR) and cordycepin in the treatment of human OSCC cells in vitro. The type of cell death, especially autophagy and apoptosis, and the underlying mechanisms were examined. We found synergistic effects of cordycepin and IR on the viability of human oral cancer cells. The combination of cordycepin and IR treatment induced apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, cordycepin induced S-phase arrest and prolonged G2/M arrest in the cells that received the combination treatment compared with those that received irradiation alone. Combined treatment induced the upregulation of ATG5 and p21 in an autophagy cascade-dependent manner, arrested the cell cycle in the G2/M phase, and repressed cell proliferation. Thus, we conclude that the combination of cordycepin and IR treatment could be a potential therapeutic strategy for OSCC.

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BACKGROUND: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment. METHODS: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored. RESULTS: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders. CONCLUSION: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.