Michael A. Kelsh

An international assessment of ovarian cancer incidence and mortality

OBJECTIVEnTo assess and characterize the temporal variation in ovarian cancer incidence and mortality by age within countries in the Americas, Europe, Asia, and Oceania.nnnMETHODS/MATERIALSnData from the National Cancer Institutes Surveillance, Epidemiology, and End Results Program in the United States (U.S.) were used to assess ovarian cancer incidence rates (1998-2008) and mortality rates, (1988-2007 for 12-month survival, 1988-2006 for 24-month survival, and 1988-2003 for 60-month survival), stratified by age at diagnosis. Data from GLOBOCAN were used to calculate country-specific incidence rates for 2010 and 2020 and case-fatality rates for 2010.nnnRESULTSnA statistically significant decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed in the U.S. for all women (-1.03%), among women who were diagnosed at <65 years of age (-1.09%) and among women who were diagnosed at ≥65 years of age (-0.95%). There was a statistically significant increase in the observed APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women; however, 5-year survival for advanced stage (III or IV) disease was low at less than 50% for women <65 years and less than 30% for women ≥65 years. Global results showed a wide range in ovarian cancer incidence rates, with China exhibiting the lowest rates and the Russian Federation and the United Kingdom exhibiting the highest rates.nnnCONCLUSIONSnOvarian cancer survival has shown modest improvement from a statistical perspective in the U.S. However, it is difficult to ascertain how clinically relevant these improvements are at the population or patient level.

Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden.

AbstractPurposenAcute lymphoblastic leukemia (ALL) is a rare hematological malignancy. With the recent introduction of a classification system for hematopoietic and lymphoid neoplasms, more comprehensive assessment of ALL epidemiology is now possible. In this study, we describe recent international incidence of ALL and project the annual number of diagnoses to 2025. We also estimate relative survival and average potential years of life lost (AYLL) to assess the societal burden of ALL.MethodsAge-specific incidence data for ALL from select cancer registries in different geographies were obtained from the International Agency for Research on Cancer’s Cancer Incidence in Five Continents Database. Country-specific age-standardized rates were calculated to allow for direct comparisons between countries. ALL-specific mortality and relative survival data were only available from the United States (US) National Cancer Institute’s Surveillance, Epidemiology, and End Results program; mortality rates were estimated for other countries.ResultsThe age-standardized incidence rate of ALL during 2003–2007 ranged from 1.08 to 2.12 per 100,000 person-years in selected countries. Incidence was generally higher in the Americas and Oceania and lower in Asia and Eastern Europe. In most countries, the incidence rate of ALL in children was approximately four times that in adults. Survival was particularly poor among adults. In selected countries, the estimated AYLL ranged from 30 to 48xa0years for all ages and from 23 to 39xa0years for adults.ConclusionsAlthough a rare disease, ALL presents a significant public health burden given poor survival outcomes among adults, AYLL, and its importance as the most common pediatric cancer.

International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia

Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990–2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment. The overall complete remission rate after first salvage was 40%, ranging from 35%–41% across disease status categories (primary refractory, relapsed with or without prior transplant), and was lower after second (21%) and third or greater (11%) salvage. The overall complete remission rate was higher for patients diagnosed from 2005 onward (45%, 95% CI: 39%–50%). One- and three-year survival rates after first, second, and third or greater salvage were 26% and 11%, 18% and 6%, and 15% and 4%, respectively, and rates were 2%–5% higher among patients diagnosed from 2005. Prognostic factors included younger age, longer duration of first remission, and lower white blood cell counts at primary diagnosis. This large dataset can provide detailed reference outcomes for patients with relapsed/refractory Ph-negative B-precursor acute lymphoblastic leukemia. clinicaltrials.gov identifier: 02003612

Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis

BACKGROUNDnWe published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis.nnnMETHODSnA comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I (2) estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures.nnnRESULTSnTen case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09).nnnCONCLUSIONSnThis meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.

Prevalence and incidence of comorbidities in elderly women with ovarian cancer.

OBJECTIVEnStudies suggest comorbidity plays an important role in ovarian cancer. We characterized the epidemiology of comorbid conditions in elderly U.S. women with ovarian cancer.nnnMETHODSnWomen with ovarian cancer age ≥66 years, and matched cancer-free women, were identified using the National Cancer Institutes Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Prevalence before diagnosis/index date and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis/index date were estimated for 34 chronic and acute conditions across a broad range of diagnostic categories.nnnRESULTSnThere were 5087 each of women with ovarian cancer and cancer-free women. The prevalence of most conditions was similar between cancer and cancer-free patients, but exceptions included hypertension (51.8% and 43.5%, respectively), osteoarthritis (13.4% and 17.3%, respectively), and cerebrovascular disease (8.0% and 9.8%, respectively). In contrast, 3- and 12-month incidence rates (per 1000 person years) of most conditions were significantly higher in cancer than in cancer-free patients: hypertension (177.3 and 47.4, respectively); thromboembolic event (145.3 and 5.5, respectively); congestive heart failure (113.3 and 28.6, respectively); infection (664.4 and 55.2, respectively); and anemia (408.3 and 33.1, respectively) at 12 months.nnnCONCLUSIONSnComorbidities were common among elderly women. After cancer diagnosis, women with ovarian cancer had a much higher incidence of comorbidities than cancer-free women. The high incidence of some of these comorbidities may be related to the cancer or its treatment, but others may have been prevalent but undiagnosed until the cancer diagnosis. The presence of comorbidities may affect treatment decisions.

Adverse Events in Adults with Relapsed or Refractory Acute LymphoblasticLeukemia (ALL): A Literature Review of Recent Clinical Trials

Background: With the introduction of new therapy options for adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL), a better understanding of existing toxicity profiles is needed. Methods: A systematic literature review was conducted to summarize the toxicity profiles in clinical trials using chemotherapeutic regimens, tyrosine kinase inhibitor (TKI)-based approaches in Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph-) R/R ALL, or other targeted therapies. Seventeen eligible articles were identified that reported toxicity profiles. We grouped adverse events into the following categories: hematological, infectious, gastrointestinal, cardiovascular/renal/hepatic, and neurological, stratified by treatment type. Treatment-related or early/induction mortality was also summarized. Results: With cytotoxic chemotherapy and its combinations, hematological adverse events were the most common, affecting virtually all patients, followed by infections, which were reported in most patients. Neurologic toxicity was the most common adverse event associated with liposomal vincristine. TKI-based treatments showed a distinct safety profile compared with the chemotherapies. Although hematological adverse events still represented the most common toxicity, infections were less common with TKI-based therapies (9-18%) than with chemotherapies (56-100%). Nausea, vomiting, and diarrhea were the predominant gastrointestinal adverse events after receipt of TKIs, whereas mucositis appeared to be more characteristic of cytotoxic chemotherapy. Conclusions: This paper provides a systematic review of the safety profile of current standard chemotherapy for adults with R/R Ph- or Ph+ ALL. Overall, documentation of adverse events was highly variable across the studies, precluding direct comparisons or pooling of results. However, this systematic literature review is the first to summarize and quantify the toxicity profiles of mainly chemotherapeutic and TKI-based regimens for adult patients with R/R ALL, providing a baseline for comparison with emerging therapies.

Prognostic impact of tumor MET expression among patients with stage IV gastric cancer: a Danish cohort study

PURPOSEnWe aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse.nnnMETHODSnThe study included archived cancer specimens from 103 stage IV gastric cancer patients (2003-2010). We analyzed MET-protein expression by immunohistochemistry (MET-positive if ≥25% of tumor cells showed MET expression). We calculated overall survival using the Kaplan-Meier method and hazard ratios comparing mortality among MET-positive and MET-negative patients using Cox regression adjusted for age, gender, and comorbidity.nnnRESULTSnWe found that 62.1% (95% confidence interval, 52.0-71.5) of patients had MET-positive tumors. Median survival was lower among patients with MET-positive tumors (3.5xa0months) than among patients with MET-negative tumors (9.6xa0months), corresponding to an adjusted hazard ratio of 2.2 (95% confidence interval, 1.3-3.7).nnnCONCLUSIONSnTumor MET expression is prevalent and has substantial prognostic impact in stage IV gastric cancer patients.