Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ~4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 ( P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.
Neutrophilic panniculitis is a relatively rare condition, characterized by predominantly neutrophilic inflammation in the subcutaneous fat. Rarely, neutrophilic panniculitis may be induced by chemotherapeutics or targeted molecular therapies, including the Bruton tyrosine kinase inhibitor ibrutinib. Previously reported cases of ibrutinib-induced panniculitis were suppressed with sustained low-dose steroid therapy while continuing ibrutinib therapy. To our knowledge, self-limiting panniculitis during ibrutinib therapy has not yet been described. We describe a case of self-limiting, neutrophilic panniculitis which developed during ibrutinib therapy. A 78-year-old woman presented to the dermatology clinic with a 3-week history of painful erythematous nodules on her lower extremities which occurred 1 month after initiating ibrutinib therapy for chronic lymphocytic leukemia. Physical examination revealed tender erythematous poorly demarcated subcutaneous nodules on the anterior and posterior aspects of both lower legs. A panniculitis was suspected clinically, and a punch biopsy was performed. Histological evaluation revealed a lobular panniculitis with fat necrosis and infiltrates consisting predominantly of neutrophils. A diagnosis of neutrophilic panniculitis was rendered, which the patient opted not to treat. The eruption waned before resolving spontaneously over the course of 6 months despite continued ibrutinib therapy. This case illustrates panniculitis as an emerging adverse drug reaction after treatment with ibrutinib and that not all cases will require ibrutinib dose adjustment or steroid therapy but rather may be subject to spontaneous resolution.
BACKGROUND Previous studies examining melanoma biopsy technique have not demonstrated an effect on overall survival. OBJECTIVE To examine overall survival of patients with cutaneous melanoma diagnosed by shave, punch, incisional, or excisional techniques from the National Cancer Database (NCDB). MATERIALS AND METHODS Melanoma data from the 2004 to 2016 NCDB data set were analyzed. A Cox proportional hazards model was constructed to assess the risk of 5-year all-cause mortality. RESULTS In total, 42,272 cases of melanoma were reviewed, with 27,899 (66%) diagnosed by shave biopsy, 8,823 (20.9%) by punch biopsy, and 5,550 (13.1%) by incisional biopsy. Both the univariate and multivariate analyses demonstrated that tumors diagnosed by incisional biopsy had significantly (p 5 .001) lower overall 5-year survival compared with shave techniques (hazard ratio [HR] 5 1.140, 95% confidence interval [CI] 1.055 to 1.231). We found no difference (p 5 .109) between shave and punch biopsy techniques (HR 1.062, or between punch and incisional techniques (HR 1.074, 95% CI 0.979-1.177, p 5 .131). CONCLUSION Incisional biopsies were associated with decreased overall 5-year survival in the NCDB. No difference was observed between shave and punch biopsy techniques. These findings support current melanoma management guidelines.
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