Cancer survivors constitute 3.5% of the United States population, but second primary malignancies among this high-risk group now account for 16% of all cancer incidence. Although few data currently ...exist regarding the molecular mechanisms for second primary cancers and other late outcomes after cancer treatment, the careful measurement and documentation of potentially carcinogenic treatments (chemotherapy and radiotherapy) provide a unique platform for in vivo research on gene–environment interactions in human carcinogenesis. We review research priorities identified during a National Cancer Institute (NCI)–sponsored workshop entitled “Cancer Survivorship—Genetic Susceptibility and Second Primary Cancers.” These priorities include 1) development of a national research infrastructure for studies of cancer survivorship; 2) creation of a coordinated system for biospecimen collection; 3) development of new technology, bioinformatics, and biomarkers; 4) design of new epidemiologic methods; and 5) development of evidence-based clinical practice guidelines. Many of the infrastructure resources and design strategies that would facilitate research in this area also provide a foundation for the study of other important nonneoplastic late effects of treatment and psychosocial concerns among cancer survivors. These research areas warrant high priority to promote NCI's goal of eliminating pain and suffering related to cancer.
This was a phase 3, randomized, double-blind, placebo-controlled study.
Adult Korean patients with essential hypertension and a baseline mean sitting clinic systolic blood pressure (scSBP) ≥150 and ...≤180 mmHg were randomized to 6-week treatment with placebo (
= 65), azilsartan medoxomil (AZL-M) 40 mg (
= 132), or AZL-M 80 mg (
= 131). The primary endpoint was the change from baseline to week 6 in trough scSBP.
The least-squares mean (standard error) change from baseline in trough scSBP in the placebo, AZL-M 40-mg, and 80-mg groups at week 6 were - 8.8 (2.00), - 22.1 (1.41), and - 23.7 (1.40) mmHg, respectively (
< 0.001 for AZL-M 40 and 80 mg vs placebo). No clinically meaningful heterogeneity in efficacy was observed between subgroups (age, sex, diabetes status) and the overall population. Treatments were well tolerated and adverse events were similar between groups.
Results of this study confirm a positive benefit-risk profile of AZL-M for essential hypertension in Korean adults.
Clinicaltrial.gov; identifier number: NCT02203916. Registered July 28, 2014 (retrospectively registered).
Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease ...(ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RH(adj) = 2.26 per log(10) IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RH(adj) = 2.57 per log(10) IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RH(adj)= 1.14 and 1.29 per log(10) IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RH(adj) = 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RH(adj)= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection.
Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children.
Sequential samples (from ...ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR.
The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones.
The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.
Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has a well-characterized efficacy and safety profile in patients with hypertension. AZL-M is approved for use in over 40 countries ...globally; however, it is not yet approved in China. Therefore, a phase 3 registration study to assess the efficacy (antihypertensive effect), safety, and tolerability of AZL-M compared with valsartan in Chinese patients with essential hypertension was undertaken.
This multicenter, double-blind, randomized, 8-week phase 3 study compared AZL-M with valsartan in Chinese patients aged ≥18 years with essential hypertension. Endpoints included change from baseline to week 8 in trough sitting clinic systolic blood pressure (scSBP) and ambulatory blood pressure monitoring parameters.
Overall, 612 patients (mean age, 57.1 years; 57.5% male) were randomized to AZL-M 80 mg (n = 209), AZL-M 40 mg (n = 199), or valsartan 160 mg (n = 204). Baseline mean scSBP was similar in all groups (157.9-158.5 mm Hg). The mean reduction in trough scSBP from baseline to week 8 was significantly greater with AZL-M 80 mg than with valsartan (-24.2 vs -20.6 mm Hg; P = .010), and noninferior with AZL-M 40 mg versus valsartan (-22.5 vs -20.6 mm Hg; P = .184). Mean reduction in 24-hour mean systolic blood pressure (n = 257) was significantly greater with both AZL-M 80 mg (-17.0 mm Hg; P < .001) and AZL-M 40 mg (-14.7 mm Hg; P = .014) than with valsartan (-9.4 mm Hg). Treatment-emergent adverse events had similar incidence (52.8%-56.5%) across the treatment groups and were generally mild or moderate. Dizziness was the most frequent treatment-related treatment-emergent adverse events (AZL-M 80 mg, 1.9%; AZL-M 40 mg, 1.5%; valsartan, 1.0%). The safety and tolerability of AZL-M were comparable with valsartan.
AZL-M was noninferior to valsartan at the 40-mg dose and superior to valsartan at the 80-mg dose in reducing trough scSBP, and showed acceptable safety-consistent with the AZL-M safety profile in other populations-in Chinese adults with hypertension.
NCT02480764.
Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare.
Sera collected during a household-based survey in rural Tanzania in 1985 were ...tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models.
Of 788 participants, 513 were aged < or = 17 years. H. pylori seropositivity increased from 76% at 0-4 years to 99% by > or = 18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2-31.4 for 10-17 vs. 0-4 years), higher birth-order (11.1; 3.6-34.1 for > or = 3rd vs. 1st born), and having a seropositive next-older sibling (2.7; 0.9-8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7-5.6), consistent with a Th2-dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3-4.4).
H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa.
An open‐label, long‐term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL‐M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with ...stage 3 chronic kidney disease. Initial therapy was AZL‐M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up‐titrated (AZL‐M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg US or 20/25 mg Europe) with other agents added during weeks 4‐52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL‐M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL‐M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long‐term follow‐up (P = .588). A greater proportion of participants up‐titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL‐M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL‐M/CLD and OLM/HCTZ showed similar efficacy and tolerability.
Background The introduction of new treatments for hairy cell leukemia has resulted in improved patient survival but also engendered increasing concern about the possibility of excess second cancers. ...The available evidence is conflicting, with most risk estimates based on sparse numbers. To our knowledge, no study has evaluated cause-specific mortality in patients with hairy cell leukemia. Methods We quantified second cancer incidence and cause-specific mortality among 3104 two-month survivors of hairy cell leukemia who were reported to 16 population-based registries in the Surveillance, Epidemiology and End Results (SEER) Program between 1973 and 2002. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were used to quantify the risk of second cancers and causes of death, respectively. The cumulative probability of a second cancer among survivors of hairy cell leukemia was calculated using a competing risk model. All statistical tests were two-sided. Results Mean follow-up of hairy cell leukemia survivors was 6.5 years (range, 2 months–29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.24, 95% confidence interval CI = 1.11 to 1.37) compared with the general population. Survivors had statistically significantly higher risks of Hodgkin lymphoma (SIR = 6.61, 95% CI = 2.13 to 15.42), non-Hodgkin lymphoma (SIR = 5.03, 95% CI = 3.77 to 6.58), and thyroid cancer (SIR = 3.56, 95% CI = 1.30 to 7.74) and a lower risk of lung cancer (SIR = 0.63, 95% CI = 0.42 to 0.90). The cumulative probability of all second cancers was estimated to be 31.9% (95% CI = 26.2 to 37.6) 25 years after hairy cell leukemia diagnosis. Among 10 000 hairy cell leukemia patients, a total excess of about 34 cancers, including 21 non-Hodgkin lymphomas, 2 Hodgkin lymphomas, and 7 solid tumors (including 2 thyroid cancers), might be observed per year. Deaths due to solid tumors were not elevated compared with the general population (SMR = 0.9), and there were statistically significant deficits in mortality due to both cardiovascular (SMR = 0.67, 95% CI = 0.56 to 0.80) and cerebrovascular (SMR = 0.61, 95% CI = 0.38 to 0.93) disease. Conclusions Patients with hairy cell leukemia are at increased risk of Hodgkin lymphoma, non-Hodgkin lymphoma, and thyroid cancer. The decrease in lung cancer incidence and smoking-associated vascular mortality may reflect an inverse association of tobacco use with hairy cell leukemia. Future studies should address the roles of immunologic impairment inherent to hairy cell leukemia, treatment modalities, and other factors as codeterminants of morbidity and mortality in hairy cell leukemia survivors.
Helicobacter pylori infection is ubiquitous, infecting close to one-half of the world's population, but its prevalence is declining in developed countries. Chronic H. pylori infection is ...etiologically linked to gastric adenocarcinoma, especially non-cardia type (63% of all stomach cancer or ~5.5% of the global cancer burden: ~25% of cancers associated with infectious etiology), and to gastric mucosal associated lymphoid tissue (MALT) lymphoma, which accounts for up to 8% of all non-Hodgkin lymphoma. Epidemiological, clinical, and animal studies have established a central role for H. pylori in gastric carcinogenesis and provided insights into the mechanisms and biologic relationships between bacterial infection, host genetics, nutrition, and environmental factors. These discoveries invite strategies to prevent infection to be the logical primary goals in a multi-pronged effort to curtail suffering and death from H. pylori infection-associated cancers.
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