Practical Role of Mutation Analysis for Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: A Meta-Analysis

Background

Imatinib has become the standard first line treatment of gastrointestinal stromal tumors (GIST) in the advanced phase and adjuvant setting. We carried out an up-to-date meta-analysis to determine the practical role of mutation analysis for imatinib treatment in patients with advanced GIST.

Methods

Eligible studies were limited to imatinib treatment for patients with advanced GIST and reported on mutation analysis. Statistical analyses were conducted to calculate the odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) using fixed-effects and random-effects models.

Results

A total of 2834 patients from 3 randomized controlled trials and 12 cohort studies were included. The ORs of response rates in KIT exon 11-mutant GISTs were 3.504 (95% CI 2.549-4.816, p<0.001) and 3.521 (95% CI 1.731-7.165, p=0.001) compared with KIT exon 9-mutant and wild type GISTs, respectively. The HRs of progression-free survival in KIT exon 11-mutant GISTs were 0.365 (95% CI 0.301-0.444, p<0.001) and 0.375 (95% CI 0.270-0.519, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. The HRs of overall survival in KIT exon 11-mutant GISTs were 0.388 (95% CI 0.293-0.515, p<0.001) and 0.400 (95% CI 0.297-0.538, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. No statistical significant differences were found between KIT exon 9-mutant and wild type. The overall response rate in KIT-exon 11-mutant GISTs were 70.5% (65%-75.9%) compared with 57.1% (51%-63.2%) in KIT-positive GISTs. No evidence of publication bias was observed.

Conclusion

Patients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Mutation analysis would be more helpful than KIT expression analysis to decide appropriate therapy for a specific patient.     

Selecting Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor with Secondary KIT Activation-Loop Domain Mutations

Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Second-line sunitinib malate (SU) therapy is largely ineffective for IM-resistant GISTs with secondary exon 17 (activation-loop domain) mutations. We established an in vitro cell-based platform consisting of a series of COS-1 cells expressing KIT cDNA constructs encoding common primary±secondary mutations observed in GISTs, to compare the activity of several commercially available tyrosine kinase inhibitors on inhibiting the phosphorylation of mutant KIT proteins at their clinically achievable plasma steady-state concentration (Css). The inhibitory efficacies on KIT exon 11/17 mutants were further validated by growth inhibition assay on GIST48 cells, and underlying molecular-structure mechanisms were investigated by molecular modeling. Our results showed that SU more effectively inhibited mutant KIT with secondary exon 13 or 14 mutations than those with secondary exon 17 mutations, as clinically indicated. On contrary, at individual Css, nilotinib and sorafenib more profoundly inhibited the phosphorylation of KIT with secondary exon 17 mutations and the growth of GIST48 cells than IM, SU, and dasatinib. Molecular modeling analysis showed fragment deletion of exon 11 and point mutation on exon 17 would lead to a shift of KIT conformational equilibrium toward active form, for which nilotinib and sorafenib bound more stably than IM and SU. In current preclinical study, nilotinib and sorafenib are more active in IM-resistant GISTs with secondary exon 17 mutation than SU that deserve further clinical investigation.     

Treating Adrenal Tumors in 26 Patients with CyberKnife: A Mono-Institutional Experience

Background

CyberKnife (CK) is a novel stereotactic radiosurgery system for treating tumors in any part of the body. It is a non-invasive or minimally invasive tumor treatment modality that can deliver high doses of spatially precise radiation and minimize exposure to neighboring healthy tissues or vital organs. The purpose of this study was to investigate the safety and efficacy of CK in the treatment of adrenal tumors.

Methods and Results

We performed a retrospective analysis of 26 patients with adrenal tumors who had been treated with CK in the radiotherapy center of our hospital between March 2009 and March 2012. Eight patients had primary adrenal tumors and 18 patients had metastatic adrenal tumors. In addition to CK, 4 patients received chemotherapy and 2 patients received immunotherapy. The average tumor volume was 72.1 cm³ and the prescribed radiation dosage ranged from 30 to 50 Gy and was fractionated 3 to 5 times with a 58% to 80% isodose line. Abdominal CT was performed between 1 to 3 months after the CK treatment to evaluate the short-term efficacy with follow-up examinations once every 3 months. Three patients had complete remission, 12 patients had partial remission, 5 patients had stable disease, and 6 patients had progressive illness. The effective rate of pain relief was 93.8% and the disease control rate was 77% with a median overall survival of 17 months and a median progression-free survival of 14 months. Treatment Related toxicity was well-tolerated, but preventative measure need to be taken for radiation enteritis.

Conclusions

CK is safe and effective for treating adrenal tumors with few adverse reactions. Nonetheless, its long-term effects requires further follow-up.     

Fractioned Dose Regimen of Sunitinib for Patients with Gastrointestinal Stromal Tumor: A Pharmacokinetic and Treatment Efficacy Study

AIM: Sunitinib has shown benefit in patients with imatinib (IM)–resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens. CONCLUSION: The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.     

Circulating Tumor Cells in Patients with Recurrent or Metastatic Head and Neck Carcinoma: Prognostic and Predictive Significance

Introduction

We investigated the frequency of detection and the prognostic and predictive significance of circulating tumor cells (CTCs) in patients with recurrent/metastatic (R/M) head and neck carcinoma (HNC) before starting systemic therapy.

Patients and methods

Using the CellSearch technology, CTCs were assessed prospectively in peripheral blood of 53 R/M-HNC patients. We performed spiking experiments to test the diagnostic performance of the CellSearch platform in identifying squamous carcinoma cells.

Results

CTCs were identified in 14 (26%) and 22 (41%) patients at baseline and at any time point, respectively. In univariate analysis ≥2 CTCs had a poorer prognostic role than 0–1 CTC. In multivariate analysis, the presence of one CTC or more was associated with a poor prognosis both in terms of progression-free survival (PFS) [Hazard Ratio (HR): 3.068, 95% confidence interval (CI): 1.53–6.13, p 0.002] and overall survival (OS) [HR: 3.0, 95% CI: 1.48–6.0, p 0.002]. A disease control after systemic therapy was obtained in 8% of CTC-positive patients as opposed to 45% in CTC-negative ones (p 0.03). The epidermal growth factor receptor (EGFR) expression was identified in 45% of CTC-positive patients.

Discussion

In conclusion, CTCs are detected in one out of three patients with RM-HNC. CTC detection is a strong prognostic parameter and may be predictive of treatment efficacy. The frequency of EGFR expression in CTCs seems to be lower than that expected in the primary tumor.     

Safety of Onartuzumab in Patients with Solid Tumors: Experience to Date from the Onartuzumab Clinical Trial Program

Background

Onartuzumab, a recombinant humanized monovalent monoclonal antibody directed against MET, the receptor for the hepatocyte growth factor, has been investigated for the treatment of solid tumors. This publication describes the safety profile of onartuzumab in patients with solid tumors using data from the global onartuzumab clinical development program.

Methods

Adverse event (AE) and laboratory data from onartuzumab phase II/III studies were analyzed and coded into standardized terms according to industry standards. The severity of AEs was assessed using the NCI Common Toxicity Criteria, Version 4. Medical Dictionary for Regulatory Activities (MedDRA) AEs were grouped using the standardized MedDRA queries (SMQs) “gastrointestinal (GI) perforation”, “embolic and thrombotic events, venous (VTE)”, and “embolic and thrombotic events, arterial (ATE)”, and the Adverse Event Group Term (AEGT) “edema.” The safety evaluable populations (patients who received at least one dose of study treatment) for each study were included in this analysis.

Results

A total of 773 onartuzumab-treated patients from seven studies (phase II, n = 6; phase III, n = 1) were included. Edema and VTEs were reported in onartuzumab-treated patients in all seven studies. Edema events in onartuzumab arms were generally grade 1–2 in severity, observed more frequently than in control arms and at incidences ranging from 25.4−65.7% for all grades and from 1.2−14.1% for grade 3. Hypoalbuminemia was also more frequent in onartuzumab arms and observed at frequencies between 77.8% and 98.3%. The highest frequencies of all grade and grade ≥3 VTE events were 30.3% and 17.2%, respectively in onartuzumab arms. The cumulative incidence of all grade ATE events ranged from 0−5.6% (grade ≥3, 0−5.1%) in onartuzumab arms. The frequency of GI perforation was below 10% in all studies; the highest estimates were observed in studies with onartuzumab plus bevacizumab for all grades (0−6.2%) and grade ≥3 (0−6.2%).

Conclusions

The frequencies of VTE, ATE, GI perforation, hypoalbuminemia, and edema in clinical studies were higher in patients receiving onartuzumab than in control arms; these are considered to be expected events in patients receiving onartuzumab.     

Results of Neurosurgical Microvascular Extracranial-Intracranial Bypass for Stroke: A Decade of Experience

In 400 patients who have had neurosurgical microvascular bypass operations by one surgeon for problems of cerebrovascular occlusion disease, the results are encouraging, particularly in those who had transient ischemic attacks with hemodynamic lesions previously considered inoperable or inaccessible. The permanent neurologic morbidity rate is 2 percent and the present operative mortality is 2.5 percent. The incidence of stroke to date on the side of a functioning bypass is 0.9 percent per year. Average duration of follow-up is 43 months.     

非小细胞肺癌脑部转移瘤适形与调强放疗的剂量研究

为探讨NSCLC脑部转移瘤调强放疗与适形放疗的剂量特点,本研究选取57例非小细胞肺癌脑转移瘤患者,其中单个脑转移灶患者5例,多个脑转移灶患者52例,分别设计全脑放疗+适形放疗与调强放疗计划,用均匀指数(HI)和适形指数(CI)评价靶区剂量,危及器官(OAR)剂量用近似最大剂量D_2%(串联)和中位剂量D_50%(并联)进行评价。研究发现,单个脑转移灶IMRT与WBRT+CRT比较中,CI为(PTV,(0.80±0.15) cGy,(0.34±0.19) cGy, p=0.00),HI为(PTV,(0.52±0.03) c Gy,(0.71±0.12) cGy, p=0.24),两者OARs剂量比较:脑干为((4 348±236) cGy,(4 593±149) cGy, p=0.01),脑垂体为((4 258±166) cGy,(4 581±123) cGy, p=0.02);在多个脑转移灶中,IMRT与WBRT+CRT比,较CI为(PTV,(0.59±0.33) cGy,(0.49±0.27) cGy, p=0.03),HI为(PTV,(0.93±0.01) cGy,(0.58±0.03) cGy, p=0.19),两者OARs剂量比较:脑干为((4 946±132) cGy,(4 843±196) cGy, p=0.51),脑垂体为((4 597±180) cGy,(4 705±149) cGy, p=0.70)。本研究的结果说明,单个脑转移灶患者,IMRT较WBRT+CRT有更好的靶区适形性、稍差的靶区异质性,脑干和垂体的IMRT剂量低于WBRT+CRT,而眼球、晶体的剂量两者差别不明显。多个脑转移灶患者,IMRT较WBRT+CRT有更好的靶区适形性、稍差的靶区异质性,而OARs剂量,IMRT较WBRT+CRT差异不明显。在临床实践过程中,应当根据患者不同的病灶情况选择合适的放疗方案,以获取更优的临床治疗效果。     

Long-Term Outcomes of Patients with Acute Cholecystitis after Successful Percutaneous Cholecystostomy Treatment and the Risk Factors for Recurrence: A Decade Experience at a Single Center

Background

Percutaneous cholecystostomy tube (PCT) has been effectively used for the treatment of acute cholecystitis (AC) for patients unsuitable for early cholecystectomy. This retrospective study investigated the recurrence rate after successful PCT treatment and factors associated with recurrence.

Methods

We reviewed patients treated with PCT for AC from October 2004 through December 2013. Patients with successful PCT treatment were those who were free from persistent PCT drainage. We used multivariable logistic regression analysis sequentially to identify factors associated with each outcome.

Results

The study included 184 patients (mean age: 70.1 years). The average duration for parenteral antibiotics was 14.4 days and 20.0 days for PCT drainage. The one-year recurrence rate was 9.2% (17/184) with most recurrences occurring within two months (6.5%, 12/184) of the procedure. Complicated cholecystitis (odds ratio [OR]: 4.67; 95% confidence interval [CI]: 1.44–15.70; P = 0.01) and PCT drainage duration >32 days (OR: 4.92; 95% CI: 1.03–23.53; P = 0.05) positively correlated with one-year recurrence; parenteral antibiotics duration >10 days (OR: 0.21; 95% CI: 0.05–0.68; P = 0.01) was inversely associated with one-year recurrence.

Conclusions

The recurrence rate was low for patients after successful PCT treatment. Predictors for recurrence included the severity of initial AC and subsequently provided treatments.     

The Clinical Effectiveness of Patient Initiated Clinics for Patients with Chronic or Recurrent Conditions Managed in Secondary Care: A Systematic Review

Background

Missed or inappropriate hospital appointments cost the UK National Health Service millions of pounds each year and delay treatment for other patients. Innovative methods of appointment scheduling that are more flexible to patient needs, may improve service quality and preserve resources.

Methods

A systematic review of the evidence for the clinical effectiveness of patient initiated clinics in managing long term care for people with chronic or recurrent conditions in secondary care. Seven databases were searched including MEDLINE, Embase and PsycINFO (using the OVID interface), the Cochrane Library of Systematic Reviews and CENTRAL, Science Citation Index Expanded, Social Sciences Citation Index, and Conference Proceedings Citation Index (via the Web of Science interface) from inception to June 2013. Studies comparing patient initiated clinics with traditional consultant-led clinics in secondary care for people with long term chronic or recurrent diseases were included. Included studies had to provide data on clinical or resource use outcomes. Data were extracted and checked by two reviewers using a piloted, standardised data extraction form.

Results

Eight studies (n = 1927 individuals) were included. All were conducted in the UK. There were few significant differences in clinical outcomes between the intervention and control groups. In some instances, using the patient initiated clinics model was associated with savings in time and resource use. The risk of harm from using the patient initiated clinic model of organising outpatient care is low. Studies with longer follow-up periods are needed to assess the long term costs and the ongoing risk of potential harms.

Conclusions

The UK policy context is ripe for evidence-based, patient-centred services to be implemented, especially where the use of health care resources can be optimised without reducing the quality of care. Implementation of patient initiated clinics should remain cautious, with importance placed on ongoing evaluation of long term outcomes and costs.     

S100P Expression Is a Novel Prognostic Factor in Hepatocellular Carcinoma and Predicts Survival in Patients with High Tumor Stage or Early Recurrent Tumors

The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry. The S100P protein was expressed in 173 of the 305 (56.7%) HCC tumors. The expression of S100P correlated with female sex (P = 0.0162), high serum α-fetoprotein level (P = 0.0001), high tumor grade (P = 0.0029), high tumor stage (P = 0.0319), the presence of the p53 mutation (P = 0.0032), and the absence of the β-catenin mutation (P = 0.0489). Patients with HCC tumors that expressed S100P were more likely to have early tumor recurrence (ETR) (P = 0.0189) and lower 5-year survival (P = 0.0023). The multivariate analysis confirmed that S100P expression was an independent prognostic factor in HCC. The combinatorial analysis showed an additive unfavorable prognostic interaction between S100P expression and the p53 mutation. In contrast, the β-catenin mutation was associated with better prognosis in both S100P-positive and -negative HCCs. Furthermore, S100P expression was a predictor of survival in HCC patients with high tumor stage or ETR (P = 0.0026 and P = 0.0002, respectively). Our study indicates the expression of the S100P protein is a novel independent predictor for poor prognosis in HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage or ETR.     

Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience

Mycopathologia - Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. We performed a...     

For or against Adjuvant Trastuzumab for pT1a-bN0M0 Breast Cancer Patients with HER2-Positive Tumors: A Meta-Analysis of Published Literatures

Background

Although the prognosis of patients with small (≤1cm) tumors is generally favorable, emerging data suggests that biological behavior varies between intrinsic subtypes in such patients. Furthermore, it still remains unclear whether HER2-positive pT1a-bN0M0 patients could benefit from adjuvant trastuzumab. For further evaluation, we sought to conduct a meta-analysis so as to get a better understanding of the prognosis for HER2-positive pT1a-bN0M0 patients and their survival benefit from adjuvant trastuzumab, accordingly, offering the implications for current practice.

Methods

The PubMed database, the online proceedings of the American Society of Clinical Oncology (ASCO) Annual Meetings, the online proceedings of the San Antonio Breast Cancer Symposium, and the CD proceedings of the International St. Gallen Breast Cancer Conference were searched for all relevant studies published before September 2012. Relative risks (RRs) were used to compare the prognosis of different intrinsic subtypes for pT1a-bN0M0 breast cancer. Analyses were also performed to estimate the association between adjuvant trastuzumab and various survival outcomes.

Results

With eight eligible studies identified, this meta-analysis demonstrated a deleterious effect of HER2+ phenotype on disease-free survival (DFS; RR = 3.677, 95% CI 2.606–5.189, p <0.001) and distant disease-free survival (DDFS; RR = 3.824, 95% CI 2.249–6.501, p<0.001) as compared to HR+/HER2- subgroup. However, significant difference failed to be achieved in terms of any endpoint between HER2+ and triple negative breast cancer (TNBC). Besides, a marked improvement in DFS was observed with the addition of trastuzumab for HER2-positive pT1a-bN0M0 patients (RR = 0.323, 95% CI 0.191–0.547, p<0.001).

Conclusion

This meta-analysis clarifies that intrinsic subtypes might be a reliable marker to predict the prognosis in pT1a-bN0M0 breast cancer. Besides, even for such early stage HER2-positive patients, adjuvant trastuzumab might bring significant survival benefit.     

Endostar Combined with Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Nasopharyngeal Carcinoma: an Update

OBJECTIVE: A previous phase-2 trial to assess the addition of Endostar to gemcitabine and cisplatin (GC) chemotherapy showed that it improves prognosis in metastatic nasopharyngeal carcinoma (M-NPC) but the study cohort was small. We wished to update that phase-2 trial by enrolling an additional 44 patients and to assess the benefit of Endostar+GC chemotherapy. METHODS: An analysis of 72 M-NPC patients treated between July 2010 and November 2016 was done. The treatment regimen was a combination of gemcitabine (1,000 mg/m²) on days 1 and 8, cisplatin (80 mg/m²) on day 1, and Endostar (15 mg/day) from day 1 to day 14 of a 21-day cycle for ≥2 cycles. The acute toxic effects and therapeutic efficacy were analyzed. RESULTS: The response rate was 77.8%. The median progression-free and overall survivals were 12 and 19.5 months, respectively. A total of 329 cycles of GC and 288 cycles of Endostar were delivered to 72 patients, with the median number of four (range, 2–10) cycles administered per patient. The main grade-3/4 hematologic toxicities were leukopenia (54.1%) and neutropenia (59.8%). The number of non-hematologic adverse events was minimal. The regimen was well-tolerated. CONCLUSIONS: Endostar+GC chemotherapy is an effective, well-tolerated regimen for M-NPC.     

Characteristics of the Delayed or Refusal Therapy in Breast Cancer Patients: A Longitudinal Population-Based Study in Taiwan

Background

The evidence indicated breast cancer was a cancer with high survival rate. However, there were still some breast cancer patients delaying or refusing therapy. So we conducted a cohort study to explore the relationship between characteristics of breast cancer patients and delay or refusal of therapy within four months after cancer diagnosed.

Methods

This was a retrospective national population-based study from 2004 to 2010 in Taiwan. This study included 35,095 patients with new diagnosis breast cancer from Taiwan Cancer Registry Database. Several analysis methods, including t test, Chi-square test, generalized estimating equations of logistic regression analysis, and Cox proportional hazards model, were performed to explore the characteristics of these patients and the relative risk of mortality with delay or refusal of therapy.

Results

Our study showed that the overall survival rates were significantly different (p <0.05) between the breast cancer patients who delayed or refused therapy and those with treatment. The patients who delayed or refused therapy had lower 5-year overall survival rate compared with the treated group. The related factors included age, Charlson comorbidity index, cancer staging (OR = 1.30–19.69; p <0.05), other catastrophic illnesses or injuries and the level of diagnostic hospitals. However, the patients with different income levels and degree of urbanization in living area were not statistically significant factors.

Conclusion

Our results demonstrated that age and cancer staging were the main patient characteristics affecting whether the patients delayed or refused therapy. The delay or refusal of treatment was associated with the level of diagnosing hospital.     

Treatment Outcomes of 257 Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Nimotuzumab Plus Intensity-Modulated Radiotherapy with or without Chemotherapy: A Single-Institution Experience

OBJECTIVES: To report the long-term outcome and toxicity of locoregionally advanced nasopharyngeal carcinoma (LA NPC) treated with nimotuzumab (h-R3) plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS: From May 2008 to March 2014, 3022 newly histology-proven, nonmetastatic NPC patients were retrospectively reviewed; among them, 257 patients treated with h-R3 were enrolled in this study. The patients' age range was between 10 and 76 years. The distribution of patients by disease stage was 150 (58.4%) in stage III, 88 (34.2%) in stage IV A, and 19 (7.4%) in stage IV B. All the patients received the treatment of h-R3 plus IMRT, and from them, 239 cases were also treated with cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox's proportional-hazard model. RESULTS: All 257 patients had completed combined treatment; 231 patients received h-R3 plus IMRT with induction chemotherapy (IC), while 26 patients received only h-R3 plus IMRT. With a median follow-up of 48 months (range, 13-75 months), the estimated 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival (OS) rates were 94.3%, 94.8%, 91.9%, 83.4%, and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage, and IC were related with OS. Multivariate analysis indicated that T stage and IC were independent prognostic factors for OS. The incidence of grade 3 to 4 acute mucositis and leukocytopenia was 10.9% and 19.8%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild to moderate at the last follow-up time. CONCLUSION: h-R3 plus IMRT with or without chemotherapy showed promising outcomes in terms of locoregional control and survival without increasing the incidence of radiation-related toxicities for patients.     

Candida Endocarditis in Patients with Candidemia: A Single-Center Experience of 14 Cases

Mycopathologia - A retrospective, single-center analysis of 14 cases of Candida endocarditis (from 355 candidemia cases during the years 2012–2019) revealed a high in-hospital mortality...     

Determinants of End-of-Life Expenditures in Patients with Oral Cancer in Taiwan: A Population-Based Study

BackgroundTo investigate the association of basic demographic data, socioeconomic status, medical services, and hospital characteristics with end-of-life expenditure in patients with oral cancer in Taiwan who died between 2009 to 2011.MethodsThis nationwide population-based, retrospective cohort study identified 5,386 patients who died from oral cancer. We evaluated medical cost in the last month of life by universal health insurance. The impact of each variable on the end-of-life expenditure was examined by hierarchical generalized linear model (HGLM) using a hospital-level random-intercept model.ResultsThe mean medical cost in the last six months of life was $2,611±3,329 (U.S. dollars). In HGLM using a random-intercept model, we found that patients younger than 65 years had an additional cost of $819 over those aged ≥65 years. Patients who had a high Charlson Comorbidity Index Score (CCIS) had an additional $616 cost over those with a low CCIS. Those who survived post-diagnosis less than 6 months had an additional $659 in expenses over those who survived more than 24 months. Medical cost was $249 more for patients who had medium to high individual SES, and $319 more for those who were treated by non-oncologists.ConclusionThis study provides useful information for decision makers in understanding end-of-life expenditure in oral cancer. We found significantly increased end-of-life expenditure in patients if they were younger than 65 years or treated by non-oncologists, or had high CCIS, medium to high individual SES, and survival of less than 6 months after diagnosis.