A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

Speech and Swallowing Rehabilitation Potentially Decreases Body Weight Loss and Improves Survival in Head and Neck Cancer Survivors.

This retrospective observational cohort study aims to assess the outcomes and associated factors in head and neck cancer (HNC) survivors with dysphagia, and to investigate the relationship between outcomes and speech and swallowing rehabilitation (SSR). We enrolled patients who were diagnosed with HNC between October 2016 and July 2018; we included 393 patients who developed dysphagia after definite treatment and were referred to speech-language pathologists (SLPs). We then classified patients into groups according to whether they received SSR. We used the clinical variables-including age, sex, site of malignancy, cancer stage, treatment modality, SSR, initial ECOG score, initial KPS, initial body weight (BW), and initial BMI-to evaluate the association between the percentage of BW change and overall survival (OS). There were 152 (39%) and 241 (61%) patients who received and did not receive SSR, respectively. In multivariate linear regression, SSR was significantly associated with percentage change in BW at 3 months post-treatment. Having SSR was positively associated with the percentage change in BW and decreased the BW loss [ß coefficient (95% CIs) = 2.53 (0.92 to 4.14)] compared to having no SSR. In the multivariate Cox regression, SSR was an independent factor for OS. Compared to no SSR, the hazard ratio (95% CIs) for patients who received SSR was 0.48 (0.31 to 0.74). SSR helps to avoid BW loss and increases overall survival. HNC patients who develop dysphagia after treatment should be encouraged to participate in SSR.

Postchemoradiotherapy systemic inflammation response index predicts treatment response and overall survival for patients with locally advanced nasopharyngeal cancer.

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.

Total Skin Treatment with Helical Arc Radiotherapy.

For widespread cutaneous lymphoma, such as mycosis fungoides or leukemia cutis, in patients with acute myeloid leukemia (AML) and for chronic myeloproliferative diseases, total skin irradiation is an efficient treatment modality for disease control. Total skin irradiation aims to homogeneously irradiate the skin of the entire body. However, the natural geometric shape and skin folding of the human body pose challenges to treatment. This article introduces treatment techniques and the evolution of total skin irradiation. Articles on total skin irradiation by helical tomotherapy and the advantages of total skin irradiation by helical tomotherapy are reviewed. Differences among each treatment technique and treatment advantages are compared. Adverse treatment effects and clinical care during irradiation and possible dose regimens are mentioned for future prospects of total skin irradiation.

Local Liver Irradiation Concurrently Versus Sequentially with Cabozantinib on the Pharmacokinetics and Biodistribution in Rats.

The aim of this study was to evaluate the radiotherapy (RT)-pharmacokinetics (PK) effect of cabozantinib in concurrent or sequential regimens with external beam radiotherapy (EBRT) or stereotactic body radiation therapy (SBRT). Concurrent and sequential regimens involving RT and cabozantinib were designed. The RT-drug interactions of cabozantinib under RT were confirmed in a free-moving rat model. The drugs were separated on an Agilent ZORBAX SB-phenyl column with a mobile phase consisting of 10 mM potassium dihydrogen phosphate (KH2PO4)-methanol solution (27:73, v/v) for cabozantinib. There were no statistically significant differences in the concentration versus time curve of cabozantinib (AUCcabozantinib) between the control group and the RT2Gy×3 f'x and RT9Gy×3 f'x groups in the concurrent and the sequential regimens. However, compared to those in the control group, the Tmax, T1/2 and MRT decreased by 72.8% (p = 0.04), 49.0% (p = 0.04) and 48.5% (p = 0.04) with RT2Gy×3 f'x in the concurrent regimen, respectively. Additionally, the T1/2 and MRT decreased by 58.8% (p = 0.01) and 57.8% (p = 0.01) in the concurrent RT9Gy×3 f'x group when compared with the control group, respectively. The biodistribution of cabozantinib in the heart increased by 271.4% (p = 0.04) and 120.0% (p = 0.04) with RT2Gy×3 f'x in the concurrent and sequential regimens compared to the concurrent regimen, respectively. Additionally, the biodistribution of cabozantinib in the heart increased by 107.1% (p = 0.01) with the RT9Gy×3 f'x sequential regimen. Compared to the RT9Gy×3 f'x concurrent regimen, the RT9Gy×3 f'x sequential regimen increased the biodistribution of cabozantinib in the heart (81.3%, p = 0.02), liver (110.5%, p = 0.02), lung (125%, p = 0.004) and kidneys (87.5%, p = 0.048). No cabozantinib was detected in the brain in any of the groups. The AUC of cabozantinib is not modulated by irradiation and is not affected by treatment strategies. However, the biodistribution of cabozantinib in the heart is modulated by off-target irradiation and SBRT doses simultaneously. The impact of the biodistribution of cabozantinib with RT9Gy×3 f'x is more significant with the sequential regimen than with the concurrent regimen.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

BACKGROUND: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. METHODS: Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. RESULTS: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). CONCLUSIONS: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Application of Carotid Duplex Ultrasonography in the Surveillance of Carotid Artery Stenosis after Neck Irradiation.

Head and neck cancer (HNC) shares some risk factors with cardiovascular disease. Neck radiotherapy (RT) causes carotid artery injury and stenosis. In HNC patients treated with RT, the prevalence rate of severe ( > 70%) carotid artery stenosis is > 10%, and the cumulative incidence continuously increases over time. There is at least a two-fold risk of cerebrovascular events in these patients compared with the normal population. Carotid artery stenosis is mainly assessed and diagnosed via duplex ultrasonography. Angioplasty and stenting may be recommended to patients who developed severe post-irradiation carotid artery stenosis. This review assessed Taiwanese data that provided some recommendations for HNC patients treated with RT. With consideration of the high prevalence rate of carotid artery stenosis after neck irradiation, duplex ultrasonography should be included in the follow-up workup.

A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation.

BACKGROUND: To analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation. METHODS: One hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed. RESULTS: The 1-year death rate for all patients was 29% [95% confidence interval (CI): 23-37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17-15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44-15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66-0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001). CONCLUSIONS: The pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.

Nutritional status at diagnosis is prognostic for pharyngeal cancer patients: a retrospective study.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. Several nutrition indicators have been reported to be related to the prognosis of HNC. However, the prognostic effect of these multiple nutrition factors in HNC is not well elucidated. The aim of this study was to evaluate the prognostic effect of these factors, including the novel hemoglobin, albumin, lymphocyte, and platelet (HALP) score, for pharyngeal cancers. MATERIAL AND METHODS: From 2008 to 2019, a total of 319 pharyngeal cancer patients were recruited. We collected adult patients with a diagnosis of nasopharyngeal carcinoma, oropharyngeal carcinoma and hypopharyngeal carcinoma. Patients who completed definite staging workup and treatment were selected for analysis. We traced nutritional and hematological parameters, including body mass index (BMI), albumin, and complete blood count, for survival analysis. RESULTS: We found that multiple nutritional markers, including BMI, hemoglobin, albumin, prognostic nutritional index (PNI), nutritional risk index (NRI) and HALP score, were important predictors for pharyngeal cancers in univariate Cox regression analysis. In multivariate analysis, we found that the HALP score was still an independent factor (HR: 1.62, 1.13-2.32 for overall survival [OS]) after adjusting of gender, age, cancer site, clinical stage, and BMI. The PNI was the most important independent factor for OS (HR: 3.12, 2.18-4.47) and cancer-specific survival (HR: 2.88, 1.88-4.41) in multivariate analysis. CONCLUSION: We found that multiple nutrition markers, including BMI, hemoglobin, albumin, PNI, NRI and HALP score, are important predictors for pharyngeal cancers. This is the first report confirming the prognostic effect of the HALP score for HNCs. Nutritional status at diagnosis should be given more attention in pharyngeal cancer patients.

Single-Institute Clinical Experiences Using Whole-Field Simultaneous Integrated Boost (SIB) Intensity-Modulated Radiotherapy (IMRT) and Sequential IMRT in Postoperative Patients With Oral Cavity Cancer (OCC).

This study aimed to review clinical experiences using whole-field simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) and sequential IMRT in postoperative patients with oral cavity cancer (OCC). From November 2006 to December 2014, a total of 182 postoperative patients with OCC who underwent either SIB-IMRT (n = 63) or sequential IMRT (n = 119) were enrolled retrospectively and matched randomly according to multiple risk factors by a computer. The differences were well balanced after patient matching (P = .38). The median follow-up time was 65 months. For patients treated with the SIB technique and the sequential technique, the respective mortality rates were 36.8% and 20.0% (P = .04). The primary recurrence rates were 26.3% and 10.0% (P = .02), respectively. The respective marginal failure rates were 26.7% and 16.7%. A multivariate logistic regression analysis showed that patients who received the SIB technique had a 2.74 times higher risk of death than those who received the sequential technique (95% confidence interval = 1.10-6.79, P = .03). Sequential IMRT provided a significantly lower dose to the esophagus (5.2 Gy, P = .02) and trachea (4.6 Gy, P = .03) than SIB-IMRT. For patients with locally advanced OCC, postoperative sequential IMRT may overcome an unpredictable geographic miss, potentially with a lower marginal failure rate in the primary area. Patients treated by sequential IMRT show equal overall survival benefits to those treated by SIB-IMRT and a lower mortality rate than those treated by SIB-IMRT. Additionally, a reduced dose to the esophagus and trachea compared to sequential IMRT was noted.

Health-related quality of life and utility in head and neck cancer survivors.

BACKGROUND: This study seeks to assess quality of life (QOL) and utility scores of head and neck cancer survivors. METHODS: We compared QOL as indicated by EORTC QLQ-C30, QLQ-H&N35, utility scores by time trade off (TTO) with previous published reference values and tested series characteristics related to global QOL and utility. RESULTS: A total of 127 patients were recruited. Of the patients, 102 (80%) completed the utility assessment. Cancer survivors had lower scores compared with norm values. Patients without a spouse had a lower utility than those with a spouse. Patients with a low annual family income also had lower global QOL and utility scores (p < 0.05). Other factors were not significantly related to QOL and utility scores. CONCLUSION: Disease and treatment of head and neck cancer lead to disability and poor health-related QOL and utility. Economic status may contribute to health-related QOL and utility, while marital status is related to utility for head and neck cancer patients.

Esophageal Metal Stents with Concurrent Chemoradiation Therapy for Locally Advanced Esophageal Cancer: Safe or Not?

BACKGROUND: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.

Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a Validated LC-MS/MS Method.

Schisandra chinensis has been used as an important component in various prescriptions in traditional Chinese medicine and, more recently, in Western-based medicine for its anti-hepatotoxic effect. The aim of this study was to develop a selective, rapid, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for pharmacokinetic studies of schizandrin in rats. Liquid-liquid extraction was used for plasma sample preparation. A UHPLC reverse-phase C18e column (100 mm × 2.1 mm, 2 µm) coupled with a mobile phase of methanol-0.1% formic acid (85:15, v/v) was used for sample separation. A triple quadrupole tandem mass spectrometer was used to detect the analytes in the selected reaction monitoring mode. The linear range of schizandrin in rat plasma was 5.0-1000 ng/mL (r² > 0.999), with a lower limit of quantification of 5 ng/mL. The method was validated with regard to accuracy, intra-day and inter-day precision, linearity, stability, recovery, and matrix effects in rat plasma, which were acceptable according to the biological method validation guidelines developed by the FDA. This method was successfully applied to a pharmacokinetic study after oral administration of 3 g/kg and 10 g/kg of Schisandra chinensis products, which yielded a maximum concentration of schizandrin of 0.08 ± 0.07 and 0.15 ± 0.09 µg/mL, respectively. A parallel study design was used to investigate the oral bioavailability of single compound of schizandrin and the herbal extract, the single compound of pure schizandrin (10 mg/kg, i.v.), pure schizandrin (10 mg/kg, p.o.), and the herbal extract of Schisandra chinensis (3 g/kg and 10 g/kg, p.o.) were given individually. The dose of Schisandra chinensis (3 g/kg) equivalent to schizandrin (5.2 mg/kg); the dose of Schisandra chinensis (10 g/kg) equivalent to schizandrin (17.3 mg/kg). The result demonstrated that the oral bioavailability of schizandrin was approximately 15.56 ± 10.47% in rats, however the oral bioavailability of herbal extract was higher than single compound. The method was successfully applied to the pharmacokinetic study of pure schizandrin after oral administration of its pharmaceutical industry products in rats.

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats.

BACKGROUND: Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT) is the most common traditional formula given to colorectal and breast cancer patients in Taiwan, according to a statistical study of the National Health Insurance Research Database. 5-Fluorouracil (5-FU) is widely used as the first line of treatment for colorectal cancer. Thus, the aim of study is to investigate the pharmacokinetic interaction of XSLJZT and 5-FU. METHODS: To investigate the herb-drug interaction of XSLJZT with 5-FU as well as its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) using pharmacokinetics, a high-performance liquid chromatography (HPLC) system coupled with a photodiode array detector was developed to monitor 5-FU and 5-FDHU levels in rat blood. Rats were divided into three cohorts, one of which was administered 5-FU (100 mg/kg, iv-intravenous) alone, while the other two groups were pretreated with low and high doses of XSLJZT (600 mg/kg/day or 2400 mg/kg/day for 5 consecutive days) in combination with 5-FU. RESULTS: The results demonstrated that 5-FU level was not significantly different between the group treated with only 5-FU and the group pretreated with a normal dose of XSLJZT (600 mg/kg/day). However, pharmacokinetic analysis revealed that pretreatment with a high dose of XSLJZT (2400 mg/kg/day) extended the residence time and increased the volume of distribution of 5-FU. No significant distinctions were found in 5-FDHU pharmacokinetic parameters at three doses of XSLJZT. CONCLUSIONS: Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice.

Identification of a Multicomponent Traditional Herbal Medicine by HPLC-MS and Electron and Light Microscopy.

BACKGROUND: Commercial pharmaceutical herbal products have enabled people to take traditional Chinese medicine (TCM) in a convenient and accessible form. However, the quantity and quality should be additionally inspected. To address the issue, a combination of chemical and physical inspection methods were developed to evaluate the amount of an herbal formula, Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT), in clinical TCM practice. METHODS: A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method with electrospray ionization was developed to measure the herbal biomarkers of guanosine, atractylenolide III, glycyrrhizic acid, dehydrocostus lactone, hesperidin, and oleanolic acid from XSLJZT. Scanning electron microscopy (SEM) photographs and light microscopy photographs with Congo red and iodine-KI staining were used to identify the cellulose fibers and starch content. Furthermore, solubility analysis, swelling power test, and crude fiber analysis were contributed to measure the starch additive in pharmaceutical products. RESULTS: The results demonstrated large variations in the chemical components of different pharmaceutical brands. The SEM photographs revealed that the starch was oval, smooth, and granular, and that the raw herbal powder appears stripy, stretched, and filiform. The stained light microscopy photographs of all of the pharmaceutical products showed added starch and raw herbal powder as extenders. CONCLUSION: The developed chemical and physical methods provide a standard operating procedure for the quantity control of the herbal pharmaceutical products of XSLJZT.

Impact of postoperative daily image-guided intensity-modulated radiotherapy on overall and local progression-free survival in patients with oral cavity cancer.

BACKGROUND: We compared the outcome of patients who received non-image-guided intensity-modulated radiotherapy (IMRT) with those who received helical tomotherapy (HT), a daily image-guided radiotherapy (IGRT), after surgery for oral cavity cancer (OCC). METHODS: During the period November 2006 to December 2013, a total of 152 postoperative OCC patients underwent either IMRT (n = 79) or daily IGRT (n = 73) 4 to 6 weeks after surgery. Patients in the IMRT group received 6 MV photon beams to 7 fields and those in the IGRT group received daily fractions of 1.8 or 2 Gy on five consecutive days. RESULTS: Patients who received daily IGRT had higher 5-year overall survival than those who received IMRT (87% versus 48%, p = 0.015). The local progression-free survival rate was also higher in patients who received IGRT (85% versus 58%, p = 0.006). More patients in the IGRT group completed the package of overall treatment time in ≤ 13 weeks and completed their course of radiation therapy in ≤ 8 weeks than patients in the IMRT group (89% versus 68%, p = 0.002; 84% versus 58%, p = 0.001), respectively. The rate of local failure in the primary tumor area was 24.0 % in the IMRT group and 6.8% in the IGRT group. Among patients with primary local failure, the marginal failure rate was 52.6% in the IMRT group and 0 % in the IGRT group. CONCLUSIONS: For patients with locally advanced OCC, postoperative IGRT results in better overall survival, better local progression-free survival, less marginal failure and shorter overall treatment time than postoperative non-image-guided IMRT.

Local pelvic irradiation modulates Pharmacokinetics of 5-Fluorouracil in the plasma but not in the Lymphatic System.

BACKGROUND: 5-fluorouracil (5-FU) is employed to enhance radiotherapy (RT) effect. Here, we evaluated the influence of whole-pelvic irradiation on the pharmacokinetics (PK) of 5-FU in plasma and lymphatic system of rats as the experimental model. METHODS: RT with 2 Gy was delivered to the whole pelvis of Sprague-Dawley rats. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. The pharmacokinetics of 5-FU in plasma and lymphatic system were calculated. RESULTS: RT at 2 Gy reduced the area under the plasma concentration vs. time curve and mean residence time of 5-FU by 21.5% and 31.5%, respectively compared with those of non-RT controls. By contrast, RT at 2 Gy increased drug clearances of 5-FU by 28.2% when compared with those of non-RT controls. There was no significant difference in T1/2, Cmax and Vss in plasma between both groups. Intriguingly, 5-Fu could be detected in the lymphatic system. In addition, the AUC in 5-FU without and with RT was 3.3-fold and 4.9-fold greater for lymph than for plasma, respectively. Compared with the non-RT group, the RT group showed increase in distribution of 5-FU in the lymphatic system (p = 0.001). CONCLUSIONS: The local whole pelvic RT at 2 Gy could modulate systemic PK of 5-FU in plasma of rats and intravenous 5-FU passing into the lymphatic system was proved. The metabolism of 5-FU might be modulated by RT but the distribution of 5-FU from blood circulation to the lymphatic system might not be changed. The RT-PK phenomena in plasma provide references for adjustment of drug administration. Chemotherapy drugs entering the lymphatic system is worthy of further investigation.

Decision-making factors affecting different family members regarding the placement of relatives in long-term care facilities.

BACKGROUND: The aim of this research was to investigate factors affecting different family members' decisions regarding the placement of relatives in long-term car (LTC) facilities in Taiwan. The objective was to investigate the correlations between family members' personal traits, the living conditions of residents in the LTC facilities, and family members' experiences with LTC facilities. METHODS: This study selected family members visiting residents in LTC facilities as research subjects and used a structured questionnaire to perform face-to-face interviews. This study used nonlinear canonical correlation analysis (OVERALS) to categorize the decision-making factors affecting family members' choices of LTC facilities. RESULTS: The results showed that when making decisions about the placement of family members, spouses chose facilities according to their own life experiences, children considered medical treatment convenience, grandchildren preferred to collect relevant information on facilities, and other relatives preferred to decide based on introductions from government departments. CONCLUSIONS: These results help clarify how different family roles affect decision-making processes regarding the choice of LTC facilities. In particular, spouses and female relatives require an interventional service mechanism that provides consultation or referral information.