Prarthana Dalal

c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target.

Purpose: This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC). Patients and Methods: This Institutional Review Board–approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses. Results: The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively. Conclusion: c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.

Research letter: Impact of pruritus on quality of life—A systematic review

To the Editor: Pruritus is a common manifestation of many dermatologic conditions. Previous research demonstrated that pruritus negatively impacts quality of life. However, the impact of pruritus is often underappreciated in dermatology and nondermatology settings, alike. We hypothesized that many of the harmful effects of pruritus that are most concerning to patients are not sufficiently addressed in the review literature read by clinicians who treat pruritus. We sought to characterize the most common patient-reported concerns related to pruritus and determine whether there was concordance with clinical review articles. This systematic reviewwas designed to identify all review articles and qualitative or mixed methods studies pertaining to the impact of pruritus on quality of life. We searched MEDLINE, Embase, and Cochrane Library from its beginning to February 1, 2015, for a combination of ‘‘prurit*’’ and ‘‘itch*’’ (*wildcard character) and ‘‘quality of life,’’ ‘‘QOL,’’ ‘‘patient burden,’’ ‘‘patient reported outcome,’’ ‘‘patient report,’’ ‘‘patient perspective,’’ and ‘‘patient centered.’’ Studies were excluded based on the title, abstract, or both if there was no indication they investigated or discussed pruritus, its impact on quality of life, or both. Therapeutic trials, animal studies, and foreign-language articles were excluded. Two reviewers, P. D. and R. K., performed data extraction and any differences were resolved by discussion. Articles were classified as original research studies if they used qualitative or mixed methods to assess primary, patient-reported data. Thematic analysis was performed in NVivo 10 (QSR International, Burlington, MA). Items were ranked based on frequency of use as a measure of how often they were addressed. The literature search yielded 1889 articles, of which 1641 did not meet inclusion criteria. In total, 248 articles were included; 224 were review articles and 24 were original research studies (Supplemental Fig 1; available at http://www.jaad.org). There were 366 and 1669 distinct items extracted from original studies (Supplemental Table I; available at http:// www.jaad.org) and review articles (Supplemental Table II; available at http://www.jaad.org), respectively. There was only partial concordance with respect to how frequently different items were

Gamma Knife Stereotactic Radiosurgery for Grade 2 Meningiomas

Purpose This study aims to report long‐term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow‐up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47‐168). The 3‐ and 5‐year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3‐ and 5‐year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Gross total resection and adjuvant radiotherapy most significant predictors of improved survival in patients with atypical meningioma

Atypical and malignant meningiomas are far less common than benign meningiomas. As aggressive lesions, they are prone to local recurrence and may lead to decreased survival. Although malignant meningiomas typically are treated with maximal surgical resection and adjuvant radiotherapy (RT), to the authors’ knowledge the optimal treatment for atypical lesions remains to be defined. There are limited prospective data in this setting.

A Comprehensive Conceptual Model of the Experience of Chronic Itch in Adults

BackgroundItch is common and often debilitating. Itch is best assessed by self-report, often using patient-reported outcome measures (PROMs). Current PROMs for itch are limited and may not capture its full impact on quality of life (QOL).ObjectiveWe sought to develop a comprehensive conceptual model of itch to improve the understanding of itch for clinicians and to serve as a framework for development of efficient and valid PROMs of itch.MethodsUsing mixed methods, including systematic review (n = 491 articles), semi-structured interviews (n = 33 adults with chronic itch with multiple etiologies), and grounded theory using a constant comparative approach, we developed a conceptual model of itch.ResultsWe found the Wilson and Cleary model to be a reasonable framework for organizing our findings. It includes five primary components: biological and physiological variables, symptom status, functional status, general health perceptions, and QOL. We propose a causal relationship beginning with the biological and physiological driving factors, with direct and indirect impacts of itch and its sequelae, including pain and sleep disturbance. These can impair function, lead to task avoidance, stigma, social life and relationship problems, emotional disturbances, and treatment burden. Together, these sequelae alter one’s perceptions of health, QOL, and treatment response.ConclusionsOur conceptual model demonstrates the profound patient-burden of itch and identifies unmet needs in the evaluation and management of itch.