Locally Advanced Non-small Cell Lung Cancer: The Past, Present, and Future

AbstractApproximately a third of patients with newly diagnosed non-small cell lung cancer (NSCLC) have locally or regionally advanced disease not amenable for surgical resection. Concurrent chemoradiation is the standard of therapy for patients with unresectable locally advanced NSCLC who have a good performance status and no significant weight loss. Prospective studies conducted over the past two decades have addressed several important questions regarding systemic therapy and thoracic radiation. They include the role of induction/consolidation chemotherapy, integration of newer chemotherapy agents with radiation and the impact of molecularly targeted agents. Improved radiation therapy techniques and precise targeting of the tumors have played a key role in this setting. Moreover, it has been shown that higher than conventional doses of thoracic radiation can be administered safely in combination with chemotherapy. This review will discuss these issues in detail and outline the strategies that need to be employed to improve the outcomes in patients with locally advanced NSCLC

PET Response-Guided Treatment of Hodgkin's Lymphoma: A Review of the Evidence and Active Clinical Trials

Risk-adaptive therapy for Hodgkin's lymphoma focuses on treatment modifications based on assessment of response. [18F]Fluoro-deoxyglucose positron emission tomography (PET) performed during or after completion of chemotherapy is a strong prognostic factor for eventual treatment outcome. Conceptually, this strategy seeks to increase efficacy and minimize toxicity through the appropriate selection of patients for either therapy escalation (high-risk, PET positive) or de-escalation (low-risk, PET negative). Preliminary evidence with tailoring both chemotherapy (drug selection, number of cycles, and dose) and radiotherapy (omission or inclusion) is varied; however, numerous clinical trials seeking to validate this approach are ongoing. This paper summarizes the available evidence and active protocols involving PET response-adapted therapy for adult (early and advanced stages) Hodgkin's lymphoma

Annual Review of Advances in Lung Cancer Clinical Research: A Report for the Year 2009

The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non-small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms

Tailoring the surface charge of dextran-based polymer coated SPIONs for modulated stem cell uptake and MRI contrast

Tracking stem cells in vivo using non-invasive techniques is critical to evaluate the efficacy and safety of stem cell therapies. Superparamagnetic iron oxide nanoparticles (SPIONs) enable cells to be tracked using magnetic resonance imaging (MRI), but to obtain detectable signal cells need to be labelled with a sufficient amount of iron oxide. For the majority of SPIONs, this can only be obtained with the use of transfection agents, which can adversely affect cell health. Here, we have synthesised a library of dextran-based polymer coated SPIONs with varying surface charge from −1.5 mV to +18.2 mV via a co-precipitation approach and investigated their ability to be directly internalised by stem cells without the need for transfection agents. The SPIONs were colloidally stable in physiological solutions. The crystalline phase of the particles was confirmed with powder X-ray diffraction and their magnetic properties were characterised using SQUID magnetometry and magnetic resonance. Increased surface charge led to six-fold increase in uptake of particles into stem cells and higher MRI contrast, with negligible change in cell viability. Cell tracking velocimetry was shown to be a more accurate method for predicting MRI contrast of stem cells compared to measuring iron oxide uptake through conventional bulk iron quantification

Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa

Background: After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. Methods: We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count $<100 cells/mm^{3}$. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing (“competing needs to healthcare”) on presentation with late-stage HIV disease. Results: Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7–4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2–2.4), were male (AOR 1.7, 95% CI 1.2–2.3), worked outside the home (AOR 1.5, 95% CI 1.1–2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1–2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0–1.9) had higher odds of late-stage HIV disease presentation. Conclusions: Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease

A randomized trial to optimize HIV/TB care in South Africa: design of the Sizanani trial

Background: Despite increases in HIV testing, only a fraction of people newly diagnosed with HIV infection enter the care system and initiate antiretroviral therapy (ART) in South Africa. We report on the design and initial enrollment of a randomized trial of a health system navigator intervention to improve linkage to HIV care and TB treatment completion in Durban, South Africa. Methods/Design We employed a multi-site randomized controlled trial design. Patients at 4 outpatient sites were enrolled prior to HIV testing. For all HIV-infected participants, routine TB screening with sputum for mycobacterial smear and culture were collected. HIV-infected participants were randomized to receive the health system navigator intervention or usual care. Participants in the navigator arm underwent a baseline interview using a strengths-based case management approach to assist in identifying barriers to entering care and devising solutions to best cope with perceived barriers. Over 4 months, participants in the navigator arm received scheduled phone and text messages. The primary outcome of the study is linkage and retention in care, assessed 9 months after enrollment. For ART-eligible participants without TB, the primary outcome is 3 months on ART as documented in the medical record; participants co-infected with TB are also eligible to meet the primary outcome of completion of 6 months of TB treatment, as documented by the TB clinic. Secondary outcomes include mortality, receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART-eligible at baseline. We hypothesize that a health system navigator can help identify and positively affect modifiable patient factors, including self-efficacy and social support, that in turn can improve linkage to and retention in HIV and TB care. Discussion We are currently evaluating the clinical impact of a novel health system navigator intervention to promote entry to and retention in HIV and TB care for people newly diagnosed with HIV. The details of this study protocol will inform clinicians, investigators, and policy makers of strategies to best support HIV-infected patients in resource-limited settings. Trial registration Clinicaltrials.gov. unique identifier: NCT01188941

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT)

Patient Disease Perceptions and Coping Strategies for Arthritis in a Developing Nation: A Qualitative Study

<p>Abstract</p> <p>Background</p> <p>There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease.</p> <p>Methods</p> <p>We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators.</p> <p>Results</p> <p>18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate). Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water.</p> <p>Conclusions</p> <p>Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world.</p

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie