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In many biomedical settings, assigning every patient the same treatment may not be optimal due to patient heterogeneity. Individualized treatment regimes have the potential to dramatically improve clinical outcomes. When the primary outcome is censored survival time, a main interest is to find optimal treatment regimes that maximize the survival probability of patients. Since the survival curve is a function of time, it is important to balance short-term and long-term benefit when assigning treatments. In this paper, we propose a doubly robust approach to estimate optimal treatment regimes that optimize a user specified function of the survival curve, including the restricted mean survival time and the median survival time. The empirical and asymptotic properties of the proposed method are investigated. The proposed method is applied to a data set from an ongoing HIV/AIDS clinical observational study conducted by the University of North Carolina (UNC) Center of AIDS Research (CFAR), and shows the proposed methods significantly improve the restricted mean time of the initial treatment duration. Finally, the proposed methods are extended to multi-stage studies.

We analyzed the improvement of survival time and the effects of neoadjuvant chemotherapy combined with radiotherapy on treating patients with advanced esophageal carcinoma. Retrospectively, 43 patients were selected with esophageal carcinoma who were administered neoadjuvant chemotherapy combined with radiotherapy. According to gender, and tumor staging, the nearest neighbor matching was carried out. Eighty-six patients (1:2) who received neoadjuvant chemotherapy and 129 patients (1:3) who underwent surgery only were taken and compared for clinical outcomes. It was found that in the combination group, the median survival time was prolonged and the 1-year survival rate improved. The diameter of tumors was significantly reduced, and the surgical resection, margin negative and total effective rates improved. In addition, the recurrence rate significantly decreased, whereas quality of life scores significantly increased (p<0.05). The comparison of overall incidence of complications was not statistically significant (p>0.05). Tumor staging, location, and diameter after neoadjuvant therapy, as well as therapeutic regimen, treatment cycle, margin negative rate and effective rate were independent risk factors for significantly influencing survival outcomes and time (p<0.05). In conclusion, neoadjuvant chemotherapy combined with radiotherapy can be utilized to treat advanced esophageal carcinoma improve survival time and promote prognosis.

This study aimed to examine the duration to achieve first blood pressure (BP) control after the diagnosis of hypertension. This was a retrospective cohort study on 195 hypertensive patients’ (age ≥18 years) records from a primary health care clinic. The median time to achieve first BP control was 7.2 months (95% confidence interval [CI] = 4.99-9.35). Cox proportional hazards regression results showed female patients were 1.5 times more likely to achieve BP control when compared with male patients (hazard ratio [HR] = 1.50, 95% CI 1.09-2.09, P = .013). Those with monotherapy were 2 times more likely (HR = 2.09, 95% CI = 1.39-3.13, P < 0.001) and those on 2 drugs were 3.5 times more likely (HR = 3.49, 95% CI = 1.65-7.40, P = .001) to achieve BP control than those with nonpharmacological treatment. The median time to achieve BP control was longer than the recommended time. Doctors may need to consider starting the pharmacological treatment early and be more aggressive in hypertensive management for male patients. [ABSTRACT FROM PUBLISHER]

Background and Aims: Clinical trials to determine the efficacy of radiotherapy (RT) in liver-confined but non-resectable Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) are scarce. We aimed to determine the benefit of RT in such tumors and investigated large HCC tumors., Methods: HCC data from the Korea Central Cancer Registry recorded from 2008 to 2010 were used. A total of 593 patients met our inclusion criteria; 67 were treated with RT while the remainder made up the non-RT group. Fifty-two RT recipients underwent combination treatments within 4 weeks after the first RT treatment, and were defined as the combination RT group. We performed propensity score matching (PSM) to compare the RT or combination RT groups with the non-RT group. The endpoint was overall survival (OS)., Results: Median follow-up time for surviving patients was 48 months. After PSM, there was no difference in OS between the RT and non-RT groups or between the combination RT and non-RT groups. However, the combination RT group had a longer median survival time (MST) (10.7 vs. 6.9 months, respectively). Next, we conducted PSM between the combination RT and non-RT groups in patients with tumor sizes ≥10 cm; MST was significantly longer in the former group (10.1 vs. 5.4 months, respectively; bootstrap 95% confidence interval of the difference in MST: 0.2-11.8)., Conclusions: As a combined modality, RT is a plausible therapeutic option for liver-confined but non-resectable BCLC stage C large HCC patients., Competing Interests: The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Objective: Our study analyzed the clinical symptoms and computed tomography (CT) manifestations of massive localized malignant pleural mesothelioma (LMPM) patients to improve the knowledge and diagnosis of this disease., Methods: Our study collected 6 massive LMPM patients pathologically confirmed by CT in the department of Radiology of the People's Hospital of Yuyao, Zhejiang Province, from January, 2007 to June, 2013; data of patients were also collected. The clinical symptoms, clinicopathological characteristics, CT manifestations, treatments and prognosis of enrolled patients were analyzed., Results: Our study enrolled 6 LMPM patients (2 males; 4 females) classified to epitheliated type (n = 4) and sarcomatous type (n = 2) with mean age of 62.7 ± 7.4, and 5 of them had a history of asbestos exposure. CT manifestations revealed that large soft-tissue mass close to pleura, which was smooth and lobulated, was discovered in all patients with maximum diameter of 10~15 cm and mean diameter of 13.67 ± 1.15 cm; The mean value of CT was 36.29 ± 2.62 HU; after enhancement, the mean value was increased to 76.36 ± 7.73 HU; patients showed zones of small patchy necrosis and large patchy necrosis. The following presentations were founded: enlargement of tumor vessel which showed arborization (2 patients), mass wrap around the descending aorta in left lower chest (1 patient), strips of fat density in mediastinum superior (1 patient), pleural tail sign (3 patients). Among 6 patients, pleural effusion (n = 4), mediastinal lymph node enlargement (n = 3), invasion and destruction of local ribs (n = 2). Median survival time of patients were 20 months (2 cases conducted operation), 24 (2 cases chose combined radiotherapy and chemotherapy) and less than 6 months (2 cases underwent chemotherapy)., Conclusion: To sum up, CT showed important diagnostic values on massive LMPM patients; patients with a history of asbestos exposure, large soft-tissue mass of pleura with an abundant blood supply and wrap around large vessels might increase the risk of massive LMPM.

A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P=0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR=1.41, 95% CI=1.08-1.84 for cardia cancer and HR=1.64, 95% CI=1.14-2.37 for intestinal-type), tumor size ≤ 5 cm (HR=1.41, 95% CI=0.56-0.99), T1 depth invasion (HR=2.34, 95% CI=1.20-4.56), lymph node metastasis (HR=1.51, 95% CI=1.19-1.96), no distant metastasis (HR=1.33, 95% CI=1.05-1.68), TNM stage III+IV (HR=1.50, 95% CI=1.13-1.98), and with chemotherapy (HR=1.53, 95% CI=1.17-1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5-6 vs. 50-60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r(2)>0.8, p<0.001). The smaller microparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both temporal and spatial factors that were determined by the characteristics of the drug delivery system. A combination of fast- and slow-releasing microparticles with 5-6 μm diameter provided favorable spatial distribution and optimal drug release for IP therapy., (© 2013.)