Differentiated Thyroid Cancer with Extrathyroidal Extension: Prognosis and the Role of External Beam Radiotherapy

A study was performed to identify variables that affected cause-specific survival (CSS) and local relapse-free rate (LRFR) in patients with differentiated thyroid cancer (DTC) and extrathyroid extension (ETE) and to examine the role of external beam radiotherapy (XRT). Prognostic factors were similar to those found in studies of all patients with DTC. In patients with postoperative gross residual disease treated with radiotherapy, 10-year CSS and LRFR were 48% and 90%. For patients with no residual or microscopic disease, 10-year CSS and LRFR were 92% and 93%. In patients older than 60 years with T3 ETE but no gross residual disease postoperatively there was an improved LRFR at 5 years of 96%, compared to 87.5% without XRT (P = .02). Patients with gross ETE benefit from XRT and there may be a potential benefit in reducing locoregional failure in patients over 60 years with minimal extrathyroidal extension (T3)

Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR

Second malignant neoplasms in patients with non hodgkin's lymphoma

A retrospective review of the records of 3886 patients with non‐Hodgkin's lymphoma registered at the Princess Margaret Hospital between 1970 and 1985 was undertaken to determine the incidence of second malignant tumours. Three thousand and twenty‐one patients with a minimum documented follow‐up of 6 months from referral were identified for analysis. The overall observed/expected ratio for all cancers in patients with malignant lymphoma was 1, suggesting no increased risk of developing a second malignant neoplasm compared to the general population. When the data were analyzed independently for each tumour site, statistically significant increased risk of developing acute non lymphocytic leukemia (ANLL) (p < 0·001) and carcinoma of the tongue (p < 0·05) were found. An increased risk of lung cancer following lymphoma was detected but was not statistically significant. Survival following diagnosis of ANLL and lung cancer was similar and significantly shorter than that following the diagnosis of other second malignancies. The risk of developing a second primary cancer was significantly related to increasing patient age

Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1–10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making

A phase II study of thalidomide and vinblastine for palliative patients with Hodgkin's lymphoma

Introduction: Patients with Hodgkin's Lymphoma (HL) who relapse or progress after primary therapy and subsequent high dose chemotherapy with autologous stem cell transplantation ( ASCT) cannot be cured with conventional treatment. We combined thalidomide (THAL), an agent with anti-angiogenic and immunomodulatory properties, with vinblastine, which is active after ASCT, to determine the objective response rate, improvement in B symptoms and toxicity in patients with refractory HD