Current treatment strategies in malignant pleural mesothelioma with a treatment algorithm

Malignant pleural mesothelioma (MPM) is a rare disease with a poor prognosis. The main therapeutic options for MPM include surgery, chemotherapy, and radiation therapy (RT). Although multimodality therapy has been reported to improve survival, not every medically operable patient is able to undergo all recommended therapy. With improvements in surgical techniques and systemic therapies, as well as advancements in RT, there has been a potential new paradigm in the management of this disease. In this review, we discuss the current literature on MPM management and propose a functional treatment algorithm

ST6GalNAc-I Promotes Lung Cancer Metastasis by Altering MUC5AC Sialylation

Lung cancer (LC) is the leading cause of cancer-related mortality. However, the molecular mechanisms associated with the development of metastasis is poorly understood. Understanding the biology of LC metastasis is critical to unveil the molecular mechanisms for designing targeted therapies. We developed two genetically engineered LC mouse models- KrasG12D ;Trp53R172H/+ ;Ad-Cre (KPA) and KrasG12D ; Ad-Cre (KA). Survival analysis showed significantly (P=0.0049) shorter survival in KPA tumor-bearing mice as compared to KA, suggesting the aggressiveness of the model. Our transcriptomic data showed high expression of St6galnac-I in KPA compared to KA tumors. ST6GalNAc-I is an O-glycosyltransferase, which catalyzes the addition of sialic acid (SA) to the initiating GalNAc residues forming sialyl Tn (STn) on glycoproteins, such as mucins. Ectopic expression of species-specific p53 mutants in the syngeneic mouse and human LC cells led to increased cell migration and high expression of ST6GalNAc-I, STn, and MUC5AC. Immunoprecipitation of MUC5AC in the ectopically expressing p53R175H cells exhibited higher affinity towards STn. In addition, ST6GalNAc-I knockout (KO) cells also showed decreased migration, possibly due to reduced glycosylation of MUC5AC as observed by low STn on the glycoprotein. Interestingly, ST6GalNAc-I KO cells injected mice developed less liver metastasis (P=0.01) compared to controls, while co-localization of MUC5AC and STn was observed in the liver metastatic tissues of control mice. Collectively, our findings support the hypothesis that mutant p53R175H mediates ST6GalNAc-I expression, leading to the sialyation of MUC5AC, and thus contribute to LC liver metastasis

Balancing Online Privacy In India

There have been disturbing press reports and articles on the Information Technology (Amendment) Act, 2008. These accounts broadly wallow about the increase in the police powers of the state. They contend that the amendment grants legal sanction to online surveillance inexorably whittling down internet privacy. This article seeks to examine this prevalent notion. It discovers that legal provisions for online surveillance, monitoring and identification of data have been inserted in a narrow and defined class of circumstances governed by tenuous procedures. At first glance it may seem that these procedures and safeguards by themselves increase the right to privacy. However, on a deeper study it is revealed that they are found wanting due to the nature of internet communications. The article takes a comprehensive look at the state of online privacy in India arising out of the Information Technology Act, 2000

Protection of Databases in India: Copyright Termination Sui Generis Conception

422-427Historically, databases are protected under copyright laws. India, which has been a major beneficiary of electronic commerce, provides copyright protections to databases. The adequacy of these protections is analysed in this paper, which considers the developments in digital, which make most of the database manufacturers susceptible to free-rider competition. The paper aims to demonstrate that adoption of the Feist doctrine by the Indian courts leads to inequitable results. The solution which the paper advocates is the adoption of a sui generis legislation which clearly prescribes the property rights and limitations, to database creators in India

Insurance Approval for Proton Beam Therapy and its Impact on Delays in Treatment

© 2018 Elsevier Inc. Purpose: Prior authorization (PA) has been widely implemented for proton beam therapy (PBT). We sought to determine the association between PA determination and patient characteristics, practice guidelines, and potential treatment delays. Methods and Materials: A single-institution retrospective analysis was performed of all patients considered for PBT between 2015 and 2018 at a National Cancer Institute–designated Comprehensive Cancer Center. Differences in treatment start times and denial rates over time were compared, and multivariable logistic regression was used to identify predictors of initial denial. Results: A total of 444 patients were considered for PBT, including 396 adult and 48 pediatric patients. The American Society for Radiation Oncology model policy supported PBT coverage for 77% of the cohort. Of adult patients requiring PA, 64% were initially denied and 32% remained denied after appeal. In patients considered for reirradiation or randomized phase 3 trial enrollment, initial denial rates were 57% and 64%, respectively. Insurance coverage was not related to diagnosis, reirradiation, trial enrollment, or the American Society for Radiation Oncology model policy guidelines, but it was related to insurance category on multivariable analysis (P \u3c .001). Over a 3-year timespan, initial denial rates increased from 55% to 74% (P = .034). PA delayed treatment start by an average of 3 weeks (and up to 4 months) for those requiring appeal (P \u3c .001) and resulted in 19% of denied patients abandoning radiation treatment altogether. Of pediatric patients, 9% were initially denied, all of whom were approved after appeal, and PA requirement did not delay treatment start (P = .47). Conclusions: PA requirements in adults represent a significant burden in initiating PBT and cause significant delays in patient care. Insurance approval is arbitrary and has become more restrictive over time, discordant with national clinical practice guidelines. Payors and providers should seek to streamline coverage policies in alignment with established guidelines to ensure appropriate and timely patient care

Insurance Approval for Proton Beam Therapy and its Impact on Delays in Treatment.

© 2018 Elsevier Inc. Purpose: Prior authorization (PA) has been widely implemented for proton beam therapy (PBT). We sought to determine the association between PA determination and patient characteristics, practice guidelines, and potential treatment delays. Methods and Materials: A single-institution retrospective analysis was performed of all patients considered for PBT between 2015 and 2018 at a National Cancer Institute–designated Comprehensive Cancer Center. Differences in treatment start times and denial rates over time were compared, and multivariable logistic regression was used to identify predictors of initial denial. Results: A total of 444 patients were considered for PBT, including 396 adult and 48 pediatric patients. The American Society for Radiation Oncology model policy supported PBT coverage for 77% of the cohort. Of adult patients requiring PA, 64% were initially denied and 32% remained denied after appeal. In patients considered for reirradiation or randomized phase 3 trial enrollment, initial denial rates were 57% and 64%, respectively. Insurance coverage was not related to diagnosis, reirradiation, trial enrollment, or the American Society for Radiation Oncology model policy guidelines, but it was related to insurance category on multivariable analysis (P \u3c .001). Over a 3-year timespan, initial denial rates increased from 55% to 74% (P = .034). PA delayed treatment start by an average of 3 weeks (and up to 4 months) for those requiring appeal (P \u3c .001) and resulted in 19% of denied patients abandoning radiation treatment altogether. Of pediatric patients, 9% were initially denied, all of whom were approved after appeal, and PA requirement did not delay treatment start (P = .47). Conclusions: PA requirements in adults represent a significant burden in initiating PBT and cause significant delays in patient care. Insurance approval is arbitrary and has become more restrictive over time, discordant with national clinical practice guidelines. Payors and providers should seek to streamline coverage policies in alignment with established guidelines to ensure appropriate and timely patient care

Five-Year Results of a Prospective Phase 2 Trial Evaluating Three-Week Hypofractionated Whole Breast Radiotherapy Inclusive of a Sequential Boost.

PURPOSE: To report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost. METHODS AND MATERIALS: Women with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis. RESULTS: Between 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer–specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast. CONCLUSIONS: Our phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients