Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome

<p>Abstract</p> <p>Background</p> <p>Current staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC.</p> <p>Methods</p> <p>A retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome.</p> <p>Results</p> <p>GTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (≧13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn ≧ 13 ml, overall survival was better after ≧4 cycles of chemotherapy than after less than 4 cycles.</p> <p>Conclusions</p> <p>The incorporation of GTVprn can provide more information to adjust treatment strategy.</p

Egy hazai matematikai felmérés eredményei nemzetközi összehasonlításban

<p><b>Comparisons of the effect of different dipeptidyl peptidase-4 inhibitor treatment for 1 year on adjusted mean changes in fasting plasma glucose (FPG) (A) and glycated hemoglobin (HbA</b>_<b>1</b><b>c) (B) in the patients with a low and high hemoglobin glycation index (HGI).</b> Factors included in the analysis of variance statistical model were baseline oral anti-diabetes drugs, age, sex and renal function. VI = vildagliptin (n = 24 in the low HGI and n = 36 in the high HGI groups), LI = linagliptin (n = 33 in the low HGI and n = 31 in the high HGI groups), SA = saxagliptin (n = 45 in low HGI and n = 64 in the high HGI groups), SI = sitagliptin (n = 97 in the low HGI and n = 138 in the high HGI group). Error bars represent 95% confidence interval (CI). p-value for between-group difference. (To convert glucose to millimoles per liter, multiply by 0.0555)</p

Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

<p>Abstract</p> <p>Background</p> <p>Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.</p> <p>Methods</p> <p>Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads.</p> <p>Results</p> <p>As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (<it>p </it>< 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (<it>p </it>= 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% <it>vs</it>. 61%; <it>p </it>< 0.001).</p> <p>Conclusions</p> <p>Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.</p

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study

BackgroundEven though advanced radiotherapy techniques provide a better protective effect on surrounding normal tissues, the late sequelae from radiation exposure to the heart are still considerable in breast cancer patients. The present population-based study explored the role of cox-regression-based hazard risk grouping and intended to stratify patients with post-irradiation long-term heart diseases.Materials and methodsThe present study investigated the Taiwan National Health Insurance (TNHI) database. From 2000 to 2017, we identified 158,798 breast cancer patients. Using a propensity score match of 1:1, we included 21,123 patients in each left and right breast irradiation cohort. Heart diseases, including heart failure (HF), ischemic heart disease (IHD), and other heart diseases (OHD), and anticancer agents, including epirubicin, doxorubicin, and trastuzumab, were included for analysis.ResultsPatients received left breast irradiation demonstrated increased risks on IHD (aHR, 1.16; 95% CI, 1.06–1.26; p &lt; 0.01) and OHD (aHR, 1.08; 95% CI, 1.01–1.15; p &lt; 0.05), but not HF (aHR, 1.11; 95% CI, 0.96–1.28; p = 0.14), when compared with patients received right breast irradiation. In patients who received left breast irradiation dose of &gt;6,040 cGy, subsequent epirubicin might have a trend to increase the risk of heart failure (aHR, 1.53; 95% CI, 0.98–2.39; p = 0.058), while doxorubicin (aHR, 0.59; 95% CI, 0.26–1.32; p = 0.19) and trastuzumab (aHR, 0.93; 95% CI, 0.33–2.62; p = 0.89) did not. Older age was the highest independent risk factor for post-irradiation long-term heart diseases.ConclusionGenerally, systemic anticancer agents are safe in conjunction with radiotherapy for managing post-operative breast cancer patients. Hazard-based risk grouping may help stratify breast cancer patients associated with post-irradiation long-term heart diseases. Notably, radiotherapy should be performed cautiously for elderly left breast cancer patients who received epirubicin. Limited irradiation dose to the heart should be critically considered. Regular monitoring of potential signs of heart failure may be conducted

Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead

New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physiochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound

The novel synthetic compound 6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells

A novel synthetic compound 6-acetyl-9-(3,4,5-trimetho-xybenzyl)-9H-pyrido[2,3-b]indole (HAC-Y6) demonstrated selective anticancer activity. In the present study, COLO 205 cells were treated with HAC-Y6 to investigate the molecular mechanisms underlying its effects. HAC-Y6 induced growth inhibition, G2/M arrest and apoptosis in COLO 205 cells with an IC50 of 0.52±0.035 µM. Annexin V/PI double staining demonstrated the presence of apoptotic cells. JC-1 staining analysis showed that HAC-Y6 decreased mitochondrial membrane potential in support of apoptosis. An immunostaining assay revealed that HAC-Y6 depolymerized microtubules. Treatment of COLO 205 cells with HAC-Y6 resulted in increased expression of BubR1 and cyclin B1 and decreased expression of aurora A, phospho-aurora A, aurora B, phospho-aurora B and phospho-H3. HAC-Y6 treatment increased protein levels of active caspase-3, caspase-9, Endo G, AIF, Apaf-1, cytochrome c and Bax, but treatment with the compound caused reduced levels of procaspase-3, procaspase-9, Bcl-xL and Bcl-2. Overall, our results suggest that HAC-Y6 exerts anticancer effects by disrupting microtubule assembly and inducing G2/M arrest, polyploidy and apoptosis via mitochondrial pathways in COLO 205 cells

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 – 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC