Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

Purpose

The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in ¹⁸F-deoxyglucose (FDG) or ¹⁸F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy.

Methods

A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting.

Results

Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n?=?73, 66 and 51 studies, and n?=?73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5?min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15?min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV_ave), to assess reproducibility, showed only a small difference in physiological uptake (?0.006?±?0.224 in 118 follow-up FDG scans and 0.09?±?0.81 in 111 follow-up FLT scans).

Conclusion

It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol.     

Informal helpers' responses when adolescents tell them about dating violence or romantic relationship problems

This study examines the responses of informal helpers to adolescents who disclose dating violence or upsetting but non-violent experiences in their romantic relationships. Based on a survey of 224 Midwestern high school students, the study found that youths were more likely to disclose problems to friends rather than others. A factor analysis of potential helpers' responses showed that, compared to avoidance and minimization, nurturing was the most typical response received. Adolescents who told someone about being victimized by severe dating violence were more likely to receive an avoidance response than those who told about less severe dating violence. Males encountered high levels of minimization regarding less severe dating violence. While friends and family seem to respond effectively to romantic relationship problems, youths need more training in how to respond helpfully to friends' difficulties with dating violence or how to encourage victims to seek help from trained practitioners.     

Measuring primary care patients' attitudes about dementia screening

OBJECTIVES: To develop a questionnaire that will capture patients' attitudes about dementia screening in primary care. METHODS: Cross-sectional study of 315 patients aged 65 and older attending urban and rural primary care clinics in Indianapolis and North Carolina. The Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) questionnaire was administered via face-to-face or telephone interview. RESULTS: The PRISM-PC questionnaire consists of two separate scales: the patient's acceptance of dementia screening scale and the patient's perceived harms and benefits of dementia screening scale. The face validity of the PRISM-PC questionnaire was based on a systematic literature review and the opinions of 16 clinician-investigators with experience in screening for dementia. Exploratory factor analyses for the acceptance scale revealed the presence of two dimensions: knowledge about dementia risk and testing for dementia. For the benefits and harms scale, exploratory factor analyses identified four dimensions: perceived benefits of screening, stigma of screening, suffering from screening, and impact of screening on patients' independence. The internal consistency of each of the above subscales was good with Cronbach's alpha ranging from 0.58-0.85. CONCLUSION: The PRISM-PC questionnaire captures primary care patients' acceptance, perceived harms, and perceived benefits of dementia screening.     

Common Integration Sites for MMTV in Viral Induced Mouse Mammary Tumors

The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. It is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genomic distances. Genes commonly affected by MMTV insertion in multiple individual tumors include, the Wnt, FGF, RSpo gene families as well as eIF3e and Notch4. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all of the features ascribed to tissue-specific stem cells.     

Age‐related fatigue resistance in the knee extensor muscles is specific to contraction mode

The question of whether skeletal muscle fatigue is preserved or enhanced in older adults is a point of controversy. Disparate findings may be attributed to differences in subject population and study protocols, including contraction mode. The purpose of this study was to test the hypotheses that healthy older (65–80 years of age, 8 males and 8 females) adults who were matched to young adults (21–35 years of age; 8 males and 8 females) with similar physical activity levels would: (1) fatigue less during isometric knee extensor (KE) contractions, but (2) would show similar fatigue during dynamic KE contractions performed at 120° s^?1. Fatigue was induced with 4 minutes of intermittent, isometric, or dynamic maximal voluntary contractions, performed on separate days. Electrically stimulated contractions were used to evaluate central activation during both fatigue protocols. Older subjects maintained a higher percentage of baseline maximum voluntary contraction (MVC) torque than young subjects during isometric contractions (mean ± SE: 71 ± 3% and 57 ± 3%, respectively, P < 0.01). In contrast, there was no difference between age groups in torque maintenance during dynamic contractions (43 ± 3% and 44 ± 3%, respectively, P = 0.86). For both groups, changes in electrically stimulated and voluntary contractions followed similar trends, suggesting that central activation did not play a role in the age‐related differences in fatigue. Fatigue during the isometric protocol was associated with fatigue during the dynamic protocol in the young group only (r = 0.62, P = 0.01), suggesting that distinct mechanisms influence fatigue during isometric and dynamic contractions in older adults. Muscle Nerve 39: 692–702, 2009     

Begin with the end in mind: the value of outcome-driven nephrology social work

The last decade has brought multiple changes in the delivery of care to patients with chronic kidney disease (CKD), and the nephrology social worker, like other members of the dialysis care team, has changed in response to a new health care climate. This article reviews a disease course perspective of CKD and the outcome-driven nephrology social work model of practice. The outcome-driven model is strategic and works toward improving patient outcomes. In this model, the social worker identifies and isolates barriers to desired treatment outcomes such as survival, quality of life, and cost containment and develops focused psychosocial interventions to reduce barriers to positive treatment outcomes. Measurement is the key to refining interventions to meet patient and clinic needs. Once an intervention is fine tuned, it can become a standard intervention in a "tool kit" that can be used by the social worker on micro- and macrolevels. This model of nephrology social work practice can improve treatment outcomes in areas such as depression management, fluid management, care planning, missed treatments, rehabilitation, satisfaction with care, and reduced hospitalizations.     

Expression of truncated Int6/eIF3e in mammary alveolar epithelium leads to persistent hyperplasia and tumorigenesis

Introduction  

Int6 has been shown to be an interactive participant with the protein translation initiation complex eIF3, the COP9 signalosome and the regulatory lid of the 26S proteasome. Insertion of mouse mammary tumor virus into the Int6 locus creates a C-terminally truncated form of the protein. Expression of the truncated form of Int6 (Int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. In addition, decreased expression of Int6/eIF3e is observed in approximately one third of all human breast carcinomas.     

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.