The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma.

Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts--including physicians, nurses, and patient advocates--to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-α2b, pegylated-interferon-α2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted.

A system-based intervention to improve colorectal cancer screening uptake.

OBJECTIVE: To determine whether mailing guaiac-based fecal occult blood tests (gFOBTs) directly to patients who are due for colorectal cancer screening would achieve higher screening uptake than using visit-based screening. STUDY DESIGN: Comparative effectiveness analysis. METHODS: We used an electronic medical record to identify 7053 New Mexico Veterans Affairs Health Care System patients aged 50 to 80 years who were due for screening in 2008. We invited 3869 randomly selected patients to participate in a randomized controlled trial comparing adherence with different fecal blood tests; 202 intervention patients were assigned to receive mailed gFOBTs. We identified the following 3 control groups who could receive only visit-based colorectal cancer screening: 3184 individuals who were not invited for the randomized controlled trial (control group 1), 2525 individuals who did not respond to invitations to participate in the randomized controlled trial (control group 2), and 255 individuals who could not be contacted (control group 3). We measured gFOBT screening within 3 months after enrollment in the intervention group, as well as gFOBT or colonoscopy screening within 6 months of identification as a control subject. We compared screening across groups using multivariate logistic regression analysis to adjust for sex, race/ethnicity, clinic site, previous gFOBT, and comorbidities. RESULTS: Colorectal screening occurred less often in each of the control groups (in 18.6% of control group 1, in 14.3% of control group 2, and in 18.8% of control group 3) than among patients mailed a gFOBT (48.5%). Adjusted odds ratios for screening among the control groups were all less than in the intervention group (adjusted odds ratios, 0.25, 0.19, and 0.23, respectively; all, P <.001). CONCLUSION: Using an electronic medical record to identify screening-eligible patients and mailing them gFOBT cards achieved higher colorectal screening uptake than performing visit-based screening.

Colorectal cancer screening adherence is higher with fecal immunochemical tests than guaiac-based fecal occult blood tests: a randomized, controlled trial.

OBJECTIVES: Determine whether colorectal cancer screening adherence is greater with fecal immunochemical tests (FIT) or guaiac-based fecal occult blood tests (gFOBT). METHODS: We used electronic health records to identify 3869 New Mexico Veterans Affairs Health Care System primary care patients due for screening in 2008 for whom fecal blood testing was appropriate. We invited randomly selected patients by mail to participate in a study comparing FIT and gFOBT. We randomly allocated 404 subjects to receive FIT (n=202) or gFOBT (n=202) by mail. We determined the proportion of subjects completing testing within 90days of agreeing to participate in the study. We also used multivariate logistic regression to evaluate screening completion, adjusting for age, gender, race/ethnicity, clinic site, previous gFOBT testing, and co-morbidity. RESULTS: Screening adherence was higher with FIT than gFOBT (61.4% vs. 50.5%, P=0.03). The adjusted odds ratio for completing FIT vs. gFOBT was 1.56, 95% CI 1.04, 2.32. CONCLUSION: In a clinic setting of patients who were due for colorectal cancer screening, adherence was significantly higher with FIT than gFOBT.

The effect of prior bisphosphonate therapy on the subsequent BMD and bone turnover response to strontium ranelate.

Strontium ranelate is an effective treatment for osteoporosis in treatment-naive women. In the United Kingdom, bisphosphonates are often used first line. Prior bisphosphonate use may blunt the bone mineral density (BMD) response to strontium ranelate by reducing strontium uptake into the bone. Sixty bisphosphonate-naive women and 60 women discontinuing bisphosphonates were recruited. All women commenced strontium ranelate and calcium/vitamin D. BMD and bone turnover markers were recorded for 12 months. After 12 months, the bisphosphonate-naive group's BMD increased by 5.6% (p < .001) at the spine, 3.4% (p < .001) at the total hip, and 4.0% (p < .001) at the heel. By comparison, the prior bisphosphonate group had a 2.1% (p = .002) increase at the spine but no change at the hip or heel. At all time points, BMD was significantly greater in the bisphosphonate-naive group. In the prior bisphosphonate group, there was no significant change in BMD during the first 6 months at the spine, but between months 6 and 12 there was a parallel gain in BMD (0.027 versus 0.020 g/cm(2), p = .40). The baseline difference in bone markers was no longer significant by 3 months for bone-specific alkaline phosphatase (BSAP) and 6 months for procollagen type 1 amino-terminal propeptide (P1NP) and carboxy-terminal cross-linking telopeptide of type I collagen (CTX). More women in the prior bisphosphonate group suffered a vertebral fracture (2 versus 8 women, p = .047). After bisphosphonates, bone turnover remains suppressed for up to 6 months, with blunting of the BMD response to strontium ranelate during this time. After 6 months, BMD increases in the spine but not at the hip or heel.

Which women should be selected for vertebral fracture assessment? Comparing different methods of targeting VFA.

Vertebral fracture assessment (VFA) is a potential screening tool for vertebral fractures, but it is uncertain how to optimize the selection of women for VFA. We investigate the use of a probability score (VFscore) to select women for VFA screening and compare this to other means of targeting VFA. We identified 1,572 treatment-naive women over age 65 who had undergone routine VFA screening. Risk factors for fracture on VFA were identified using multivariate logistic regression, and a VFscore was created. Different thresholds of VFscore were examined and compared to using BMD as a means of targeting screening. After multivariate logistic regression, the risk factors significantly associated with the presence of a fracture on VFA were age, femoral neck BMD, prior clinical fracture, and height loss/kyphosis. The VFscore derived from these factors had a 65.5% sensitivity and a 65.5% specificity for determining vertebral fracture status. For equal resource requirements, the VFscore identified more women with fracture than using BMD category to target VFA. Compared to routinely screening all women, VFscore enabled a 30% reduction in the number of women undergoing VFA while still identifying >90% of women with a vertebral fracture. Overall, a large proportion of the population is required to undergo VFA in order to ensure that the majority of women with a vertebral fracture are selected for screening. The VFscore increased the efficiency of VFA screening to a modest degree compared to screening routinely or according to BMD category.

Vertebral morphometry by DXA: a comparison of supine lateral and decubitus lateral densitometers.

Identification of vertebral fracture has become increasingly important in the diagnosis and management of osteoporosis. This study compares the morphometric techniques on a fan beam dual-energy X-ray absorptiometry (DXA) GE-Lunar Expert system (Expert) using a supine lateral position and a narrow fan beam GE-Lunar Prodigy system (Prodigy; GE Lunar, Madison, WI) that requires lateral decubitus positioning. Patient acceptability, image quality, observer, and equipment variability were determined. Study subjects were recruited from clinical referrals sent for a routine DXA study that included vertebral morphometry. Twenty-five patients underwent lateral vertebral assessment on both machines and completed a questionnaire on comfort and tolerability. Analysis was undertaken by two trained observers. Vertebral height, anterior/posterior height (A/P) and mid/posterior height (M/P) ratios, image quality, and prevalent fractures were assessed. There were no significant differences in patient comfort or image quality scores. More upper thoracic vertebrae could be assessed on the Expert, and good radiographic positioning was easier to achieve on the Expert. Inter-observer coefficients of variance percentage (CV%) of vertebral height was lower on the Prodigy (3.5% in the lumbar spine rising to 12.8% in the thoracic spine) than the Expert (4.2% to 16.9%). Inter-observer CV% for A/P and M/P ratios varied from 2.5% to 10.5% on the Prodigy compared with 3.5% to 12.3% on the Expert, depending on vertebral level. The variation between instruments was similar to the inter-observer CV% (anterior height: -0.11+/-1.65 mm; mid height: 0.54+/-1.51 mm; posterior height: 0.43+/-1.46 mm). There was good agreement between observers and between the Expert and Prodigy in identifying severe fractures, but lack of agreement in identifying moderate fractures. In conclusion, there was no clinically significant difference in patient comfort and image quality between the Expert and the Prodigy. The inter-observer variations in vertebral height and A/P and M/P ratios are similar to the variations between instruments. In making the change from the supine lateral to the decubitus lateral positioning, measurements of vertebral height are reproducible and patient comfort is not compromised.

Bone mineral density and depot medroxyprogesterone acetate.

INTRODUCTION: Depot medroxyprogesterone acetate (DMPA) suppresses pituitary gonadotrophin output, thus, suppressing ovulation. Estrogen production from the ovary is also strongly inhibited, and the resulting estrogen deficiency has a detrimental impact on bone. Depot medroxyprogesterone acetate may be particularly detrimental in young women, as it may impede attainment of peak bone mass, and switching to a different contraceptive is recommended. However, the effect of sequential use of DMPA with other contraceptives in this age group has not been investigated. METHODS: This was a cross-sectional analysis of 218 DMPA users who were 20 years or older (mean, 31 years, +/-8.9 SD) at the time of bone mineral density (BMD) estimation. The majority of women had used one or more contraceptive beside DMPA. The most commonly used alternative contraceptive was the oral combined pill (OCP). It was used by 65% of women (n=143) and for an average duration of 6 years. A logistic regression model was used to estimate the association between potential risk factors and low bone mass. RESULTS: The prevalence of low bone mass at either hip or spine (T< or =1) was 41%. The prevalence of a T score below -2.5 was 5%, and 45% of women had already sustained one fracture. Younger age was associated with higher BMD [odds ratios (ORs), 0.054; 95% confidence interval (CI), 0.007-0.431]. However, this protective effect of age was lost once the interaction between the duration of both DMPA and OCP was introduced into the model (OR for low BMD, 1.42; 95% CI, 1.09-1.8). The use of DMPA first before ever use of OCP was particularly detrimental to BMD (OR, 3.94; 95% CI, 1.08-14.0). On the contrary, body mass index was positively associated with BMD (OR, 0.86; 95% CI, 0.8-0.9). No other demographic or anamnestic variables significantly predicted the presence of low BMD in this group of young women. This group of DMPA users appear to be at a very high risk of both low BMD and fractures, possibly independently of DMPA use. This needs to be considered when writing guidelines for risk assessment. CONCLUSION: The use of DMPA before achievement of peak bone mass may be particularly detrimental to bone, but switching DMPA with the OCP in these women does not seem to confer specific benefit in terms of bone density. This needs to be taken into consideration when a change in contraceptive is considered purely for the sake of bone protection.

Hyperparathyroidism in elderly osteopenic women.

Raised levels of parathyroid hormones (PTH) predispose to osteoporotic fracture particularly in the elderly. The true prevalence of primary or secondary hyperparathyroidism is unknown, as PTH evaluation is not performed as a screening test in the elderly. We report raised PTH levels in 27 of 190 (14.2%) community living fully mobile postmenopausal women with densitometrically established osteopenia, consuming an average of 645 (+/-191) mg of calcium per day. Twenty-five of the 27 women with raised PTH were normocalcaemic, hypercalcaemia been found only in two. Serum 25 hydroxy vitamin D levels were all within the normal range (above 22 nmol/l). Women with a raised PTH were significantly older and their serum 25 hydroxy vitamin D levels were significantly lower than those women with normal PTH values. These data suggest that in community leaving healthy postmenopausal women, normocalcaemic hyperparathyroidism, in the presence of what are still considered normal vitamin D levels, may be common. This may suggests that widespread supplementation with calcium and vitamin D may be required in postmenopausal women for PTH suppression and preservation of bone mass.