Citations

SummaryDickkopf‐1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti‐DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma‐related bone disease and as an agent with potential anti‐myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose‐limiting toxicity (DLT) of escalating doses in combination with anti‐myeloma therapy and zoledronic acid. Twenty‐eight patients were enrolled and received BHQ880 at doses of 3–40 mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal‐related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti‐myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.

AbstractA possible causal relationship between sarcoidosis and malignancy has been the subject of debates for decades. To better understand this association, we conducted a systematic review and meta‐analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence interval (CI) comparing the incidence of malignancy in patients with sarcoidosis versus non‐sarcoidosis participants. Pooled risk ratios (RR) and 95% CI were calculated using a random‐effect, generic inverse variance methodology. Five studies were identified and included in our data analyses. The pooled RR of malignancy in patients with sarcoidosis was 1.21 (95% CI: 1.04–1.40). However, when we performed a sensitivity analysis that included only studies that compared the incidence of malignancy after the first year of the diagnosis of sarcoidosis with the incidence of malignancy after the first year of index date for non‐sarcoidosis controls, the pooled risk ratio decreased and did not reach statistical significance (RR 1.13, 95% CI: 0.97–1.32). Furthermore, analysis for publication bias has suggested that publication bias in favour of positive studies may be present. In conclusion, after accounting for possible detection bias and publication bias, there does not appear be a significant association between sarcoidosis and malignancy.

AbstractThe number of available genetic testing options and the nuances associated with these options continue to expand. In addition, the scope of genetic testing has broadened to areas and specialties beyond Medical Genetics. In response to these changes, diagnostic laboratories have employed genetic counselors to help navigate the increasing complexity of genetic testing, given their expertise and training in human genetics. However a largely unrecognized aspect of this role involves the use of counseling skills. Counseling skills are used by laboratory genetic counselors in a variety of situations to convey information and facilitate understanding among clinicians and medical staff. This helps to reduce test ordering errors, promote optimal test utilization, and ensure best patient care practices. The specific counseling skills used by laboratory counselors will be explored using three fictional case vignettes, followed by a discussion of the applicability of these skills in other contexts. Exploration of the unique ways in which laboratory genetic counselors apply their counseling skills can be useful for professional development and instructive for graduate training programs.

Purpose ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. Methods We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Results Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Conclusion Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Purpose Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods Eligible patients were adults with newly diagnosed untreated stages II to IV CD20 + DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.