Selected cancers with increasing mortality rates by educational attainment in 26 states in the United States, 1993–2007

Background

Mortality rates continue to increase for liver, esophagus, and pancreatic cancers in non-Hispanic whites and for liver cancer in non-Hispanic blacks. However, the extent to which trends vary by socioeconomic status (SES) is unknown.

Methods

We calculated age-standardized death rates for liver, esophagus, and pancreas cancers for non-Hispanic whites and non-Hispanic blacks aged 25–64 years by sex and level of education (≤12, 13–15, and ≥16 years, as a SES proxy) during 1993–2007 using mortality data from 26 states with consistent education information on death certificates. Temporal trends were evaluated using log-linear regression, and rate ratios (RRs) with 95 % confidence intervals (CIs) compared death rates in persons with ≤12 versus ≥16 years of education.

Results

Generally, death rates increased for cancers of the liver, esophagus, and pancreas in non-Hispanic whites and non-Hispanic blacks (liver cancer only) with ≤12 and 13–15 years of education, with steeper increases in the least educated group. In contrast, rates remained stable in persons with ≥16 years of education. During 1993–2007, the RR (rates in ≤12 versus ≥16 years of education) increased for all three cancers, particularly for liver cancer among men which increased from 1.76 (95 % CI, 1.38–2.25) to 3.23 (95 % CI, 2.78–3.75) in non-Hispanic whites and from 1.28 (95 % CI, 0.71–2.30) to 3.64 (95 % CI, 2.44–5.44) in non-Hispanic blacks.

Conclusions

The recent increase in mortality rates for liver, esophagus, and pancreatic cancers in non-Hispanic whites and for liver cancer in non-Hispanic blacks reflects increases among those with lower education levels.     

Disparities in survival improvement for metastatic colorectal cancer by race/ethnicity and age in the United States

Purpose

Previous studies documented significant increase in overall survival for metastatic colorectal cancer (CRC) since the late 1990s coinciding with the introduction and dissemination of new treatments. We examined whether this survival increase differed across major racial/ethnic populations and age groups.

Methods

We identified patients diagnosed with primary metastatic colorectal cancer during 1992–2009 from 13 population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, which cover about 14 % of the US population. The 5-year cause-specific survival rates were calculated using SEER*Stat software.

Results

From 1992–1997 to 2004–2009, 5-year cause-specific survival rates increased significantly from 9.8 % (95 % CI 9.2–10.4) to 15.7 % (95 % CI 14.7–16.6) in non-Hispanic whites and from 11.4 % (95 % CI 9.4–13.6) to 17.7 % (95 % CI 15.1–20.5) in non-Hispanic Asians, but not in non-Hispanic blacks [from 8.6 % (95 % CI 7.2–10.1) to 9.8 % (95 % CI 8.1–11.8)] or Hispanics [from 14.0 % (95 % CI 11.8–16.3) to 16.4 % (95 % CI 14.0–19.0)]. By age group, survival rates increased significantly for the 20–64-year age group and 65 years or older age group in non-Hispanic whites, although the improvement in the older non-Hispanic whites was substantially smaller. Rates also increased in non-Hispanic Asians for the 20–64-year age group although marginally nonsignificant. In contrast, survival rates did not show significant increases in both younger and older age groups in non-Hispanic blacks and Hispanics.

Conclusion

Non-Hispanic blacks, Hispanics, and older patients diagnosed with metastatic CRC have not equally benefitted from the introduction and dissemination of new treatments.     

Assessing environmental and occupational risk factors for lung cancer in Mexican–Americans

Background

We investigated environmental and occupational exposures and smoking history (while controlling for demographics) in a population of Mexican–American lung cancer cases and controls from the Houston metropolitan area.

Methods

Data were collected between 1991 and 2005 as part of an on-going multi-racial/ethnic, lung cancer case–control study. Cases included 212 Mexican–American lung cancer cases from UT MD Anderson Cancer Center. Controls (n = 328) were recruited from Houston’s largest multispecialty group practice and frequency matched to the cases by age (±5 years), sex, and ethnicity. Environmental and occupational factors were analyzed and odds ratios and 95% confidence intervals were calculated using logistic regression.

Results

We detected elevated risks of lung cancer associated with pesticide exposure and found conventional and antimicrobial (e.g., sterilizers, disinfectants, antiseptics) pesticides were associated with an increased risk of lung cancer in Mexican–Americans (conventional pesticides and antimicrobial pesticides combined: OR = 1.80, 95% CI 1.13–2.86; conventional pesticides: OR = 2.05, 95% CI 1.23–2.39; antimicrobial pesticides: OR = 2.48, 95% CI 1.46–4.21).

Conclusions

Although we found over a two-fold increased risk of lung cancer among Mexican–Americans for pesticides, we could not identify individual pesticides. Our findings are an important preliminary step in identifying factors that are specifically associated with lung cancer risk among Mexican Americans.     

Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women

Purpose

Common analgesics (aspirin, non-aspirin NSAIDs, and acetaminophen) may be associated with hormone-related cancers, possibly via effects on sex hormone and prolactin concentrations.

Methods

Between 1996 and 1999, 29,611 participants in the Nurses’ Health Study II (NHSII) provided blood samples; 18,521 provided samples timed in the early follicular and mid-luteal phases of the menstrual cycle, the remainder provided untimed samples. We assessed the cross-sectional relationship between analgesic use and plasma sex hormone and prolactin concentrations among 2,034 premenopausal women, 32–54 years old, who served as controls in nested case–control studies, or participated in a within-person hormone reproducibility study in the NHSII; this included 1,700 timed and 334 untimed samples. Estrogens and progesterone were measured in timed samples; androgens and prolactin were measured in timed and untimed samples.

Results

In multivariable models, non-aspirin NSAIDs were positively associated with follicular free estradiol [13.5 % higher, use ≥4 days/week vs. nonusers (p = 0.04; p _trend = 0.11)]; results for follicular total estradiol were similar (13.2 % higher, p = 0.06; p _trend = 0.11). Acetaminophen use was inversely associated with prolactin (11.8 % lower, use 2 days/week vs. nonusers, p = 0.01, p _trend = 0.04). Acetaminophen was also inversely associated with free testosterone (7.1 % lower, use 2 days/week vs. nonusers, p = 0.04; p _trend = 0.04). No other associations were observed with the other hormones, or with aspirin use.

Conclusions

There were no clear patterns between analgesic use and sex hormones in premenopausal women. Acetaminophen use may be modestly associated with prolactin and free testosterone. Our results do not support that analgesic use influences cancer risk through alterations in premenopausal circulating sex hormones or prolactin.     

A trend analysis of breast cancer incidence rates in the United States from 2000 to 2009 shows a recent increase

Recent reports have shown that the breast cancer incidence rate in the US stabilized after a sharp reduction in 2002 and 2003. It is important to continue monitoring breast cancer incidence rates according to age group, race/ethnicity, estrogen receptor (ER) status, and tumor stage. Age-standardized breast cancer incidence rates were calculated using data from the surveillance, epidemiology, and end results 18 registries from 2000 to 2009, for 677,774 female breast cancer patients aged 20 and above. Jointpoint regression models were used to fit a series of joined straight lines on a log scale to annual age-standardized rates. The incidence rates of all breast cancer significantly increased for non-Hispanic blacks from 2005 to 2009 (annual percentage change, APC = 2.0 %, p = 0.01) and Asian/Pacific Islanders from 2000 to 2009 (APC = 1.2 %, p = 0.02). Since 2004, incidence rates in women aged 40–49 years significantly increased for most racial/ethnic groups (overall APC = 1.1 %, p = 0.001). The incidence rate of carcinoma in situ significantly increased in all racial/ethnic groups, with an APC range from 2.3 to 3.0 % (p < 0.005). The localized breast cancer incidence significantly increased in non-Hispanic blacks (APC = 1.3 %, p = 0.004) and Asians (APC = 1.2 %, p = 0.03). ER-positive breast cancer significantly increased in almost all age/race sub-groups after 2005 (APC by race: non-Hispanic whites 1.5 %, non-Hispanic blacks 4.3 %, Asian/Pacific Islanders 1.7 %, and Hispanics 1.8 %; all p values <0.05), while ER-negative breast cancer decreased in most sub-groups (APC by race: non-Hispanic whites—3.9 %, non-Hispanic blacks—3.7 %, Asian/Pacific Islanders—1.5 %, and Hispanics—4.3 %; all p values <0.05). Recently the incidence of breast cancer appears to be increasing in certain subgroups, including ER-positive, early-stage breast cancers, in particular among non-Hispanic blacks and Asian/Pacific Islanders. Further studies are warranted to examine possible reasons for these changes, such as changes in mammography screening methods and risk factors prevalence.     

Disparities in survival after female breast cancer diagnosis: a population-based study

Background

Despite advances in treatment and increased screening, female breast cancer survival is affected by race, ethnicity, and socioeconomic status (SES). The purpose of this study was to substantiate disparities in breast cancer mortality in a large and unique dataset containing 7 distinct racial groups, 31 comorbidities, demographic and clinical/pathological patient characteristics, and neighborhood poverty information.

Methods

Florida Cancer Data System registry (1996–2007) linked with the Agency for Health Care Administration and U.S. Census tract (n = 127,754) explored median survival and 1-, 3-, and 5-year survival rates by the Kaplan–Meier method. Log-rank tests compared survival curves by race/ethnicity/SES. Cox proportional hazards regression models were used to obtain unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals.

Results

Native Americans had the lowest median survival (7.4 years) and Asians had the highest (12.6 years). For the univariate analysis, worse survival was seen for blacks (HR = 1.44; p < 0.001) and better survival for Asians (HR = 0.71; p < 0.001), Asian Indians or Pakistanis (HR = 0.65; p = 0.013), and Hispanics (HR = 0.92; p < 0.001). Multivariate analysis demonstrated sustained survival detriment for blacks (HR = 1.28; p < 0.001) and improved survival for Hispanics (HR = 0.90; p = 0.001). For SES, there was an incremental improvement in survival for each higher SES category in all analyses (p < 0.001).

Conclusions

Utilizing a large enriched state cancer registry controlling for multiple demographic, clinical, and comorbidities, we fully explored survival disparities in female breast cancer and found certain aspects of race, ethnicity, and SES to remain significantly associated with breast cancer survival. More research is needed to uncover the source of these ongoing disparities.     

Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study

Purpose

Common germline variation in the 5′ region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians.

Methods

We genotyped nine single nucleotide polymorphisms (SNPs) within six miRNA gene regions previously associated with breast cancer, in 1,972 cases and 1,776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to evaluate SNP association with breast cancer risk. Additionally, hazard ratios (HRs) for breast cancer-specific mortality were estimated.

Results

Two miR-185 SNPs provided suggestive evidence of an inverse association with breast cancer risk (rs2008591, OR = 0.72 (95 % CI = 0.53–0.98, p value = 0.04) and rs887205, OR = 0.71 (95 % CI = 0.52–0.96, p value = 0.03), respectively) among African Americans. Two SNPs, miR-34b/34c (rs4938723, HR = 0.57 (95 % CI = 0.37–0.89, p value = 0.01)) and miR-206 (rs6920648, HR = 0.77 (95 % CI = 0.61–0.97, p value = 0.02)), provided evidence of association with breast cancer survival. Further adjustment for stage resulted in more modest associations with survival (HR = 0.65 [95 % CI = 0.42–1.02, p value = 0.06] and HR = 0.79 [95 % CI = 0.62–1.00, p value = 0.05, respectively]).

Conclusions

Our results suggest that germline variation in the 5′ region proximal to pre-miRNA gene sequences may be associated with breast cancer risk among African Americans and breast cancer-specific survival generally; however, further validation is needed to confirm these findings.     

Association between endogenous sex steroid hormones and insulin-like growth factor proteins in US men

Purpose

Sex steroid hormone concentrations and insulin-like growth factor (IGF) proteins have been independently associated with risk of cancer, chronic diseases, and mortality. However, studies that evaluated the inter-relation between the sex hormones and IGF pathways have provided mixed results. We examined the association between endogenous sex hormones and sex hormone-binding globulin (SHBG) with IGF-1 and IGF-binding protein 3 (IGFBP-3) in a population-based sample of US men.

Methods

Data from 1,135 men aged 20 years or older participating in the third National Health and Nutrition Examination Survey (NHANES III) were analyzed. Weighted linear regression was used to estimate geometric means and 95 % confidence intervals for IGF-1 and IGFBP-3 concentrations by sex steroid hormones and SHBG after adjusting for age, race/ethnicity, body mass index, waist circumference, alcohol consumption, cigarette smoking, physical activity, diabetes, and mutually adjusting for other sex hormones and SHBG.

Results

No significant association was observed between sex steroid hormones, SHBG, and IGF-1 concentrations. Total estradiol (% difference in Q5 ? Q1 geometric means ?9.7 %; P-trend 0.05) and SHBG (% difference ?7.3 %; P-trend 0.02) were modestly inversely associated with IGFBP-3. Total testosterone was modestly inversely associated with IGFBP-3 (% difference ?6.2 %; P-trend 0.01), but this association disappeared after adjustment for total estradiol and SHBG (% difference 2.6 %; P-trend 0.23). Androstanediol glucuronide was not associated with IGFBP-3.

Conclusions

These findings suggest that there may be inter-relationships between circulating total estradiol, SHBG, and IGFBP-3 concentrations. Future research may consider these inter-relationships when evaluating potential joint effects of the sex hormones and IGF pathways.     

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort

Purpose

Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations.

Methods

A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case–control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA.

Results

In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %.

Conclusions

Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.     

Population-based assessment of racial/ethnic differences in utilization of radical cystectomy for patients diagnosed with bladder cancer

Purpose

Radical cystectomy is a surgical treatment for recurrent non-muscle-invasive and muscle-invasive bladder cancer; however, many patients may not receive this treatment.

Methods

A total of 27,578 patients diagnosed with clinical stage I–IV bladder cancer from 1 January 2007 to 31 December 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry database. We used multivariable regression analyses to identify factors predicting the use of radical cystectomy and pelvic lymph node dissection. Cox proportional hazards models were used to analyze survival outcomes.

Results

A total of 1,693 (6.1%) patients with bladder cancer underwent radical cystectomy. Most patients (92.4%) who underwent radical cystectomy also underwent pelvic lymph node dissection. When compared with white patients, non-Hispanic blacks were less likely to undergo a radical cystectomy [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. Moreover, recent year of surgery 2013 versus 2007 (OR 2.32, 95% CI 1.90–2.83, p < 0.001), greater percentage of college education ≥36.3 versus <21.3% (OR 1.23, 95% CI 1.04–1.44, p = 0.013), Midwest versus West (OR 1.64, 95% CI 1.39–1.94, p < 0.001), and more advanced clinical stage III versus I (OR 29.1, 95% CI 23.9–35.3, p < 0.001) were associated with increased use of radical cystectomy. Overall survival was improved for patients who underwent radical cystectomy compared with those who did not undergo a radical cystectomy (hazard ratio 0.88, 95% CI 0.80–0.97, p = 0.008).

Conclusion

There is significant underutilization of radical cystectomy in patients across all age groups diagnosed with bladder cancer, especially among older, non-Hispanic black patients.

     

Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up

Plasma estrogen and androgen levels are positively associated with postmenopausal breast cancer risk, but how long a single blood measurement can predict risk and whether the associations vary by tumor hormone receptor status remain unclear. We conducted nested case–control analyses within the Nurses’ Health Study. Blood samples were collected in 1989–1990 and again in 2000–2002. Among postmenopausal women not using postmenopausal hormones at blood collection, 707 cases were diagnosed through June 2010, with two matched controls per case. We used unconditional logistic regression analyses to estimate the relative risks controlling for other breast cancer risk factors. The intra-class correlation coefficients for two blood measurements collected 10 years apart ranged from 0.54 (dehydroepiandrosterone sulfate, DHEAS) to 0.74 (sex hormone-binding globulin, SHBG). Overall, women in the top (vs. bottom) 25 % of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS were at a 50–110 % higher risk of breast cancer (p _trend < 0.001). SHBG was inversely associated with risk (p _trend = 0.004). RRs were similar when comparing cases diagnosed 1–10 versus 11–20 years (or 16–20 years) after blood collection (p _interaction > 0.2). Except for DHEAS, the associations varied significantly by hormone receptor status (p _{heterogeneity} ≤ 0.02). For example, the RRs (95 % CIs) comparing the highest versus lowest quartile were 2.8 (2.0–4.0; p _trend < 0.001) for ER +/PR + tumors versus 1.1 (0.6–2.1; p _trend = 0.98) for ER?/PR? tumors for estradiol, and 1.8 (1.3–2.5; p _trend < 0.001) versus 0.6 (0.3–1.2; p _trend = 0.35) for testosterone. One measure of circulating sex hormones in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 16–20 years.     

Anthropometric, behavioral, and female reproductive factors and risk of multiple myeloma: a pooled analysis

Background

Risk of developing multiple myeloma (MM) rises with age and is greater among men and blacks than among women and whites, respectively, and possibly increased among obese persons. Other risk factors remain poorly understood. By pooling data from two complementary epidemiologic studies, we assessed whether obesity, smoking, or alcohol consumption alters MM risk and whether female reproductive history might explain the lower occurrence of MM in females than in males.

Methods

The Los Angeles County MM Case–Control Study (1985–1992) included 278 incident cases and 278 controls, matched on age, sex, race, and neighborhood of residence at case’s diagnosis. We estimated MM risk using conditional logistic regression to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). In the prospective California Teachers Study (CTS), 152 women were diagnosed with incident MM between 1995 and 2009; we calculated hazard ratios using Cox proportional hazards analysis. Data from the two studies were pooled using a stratified, nested case–control sampling scheme (10:1 match) for the CTS; conditional logistic regression among 430 cases and 1,798 matched controls was conducted.

Results

Obesity and smoking were not associated with MM risk in the individual or combined studies. Alcohol consumption was associated with decreased MM risk among whites only (pooled OR = 0.66, 95 % CI = 0.49–0.90) for ever versus never drinking. Higher gravidity and parity were associated with increased MM risk, with pooled ORs of 1.38 (95 % CI = 1.01–1.90) for ≥3 versus 1–2 pregnancies and 1.50 (95 % CI = 1.09–2.06) for ≥3 versus 1–2 live births.

Conclusions

Female reproductive history may modestly alter MM risk, but appears unlikely to explain the sex disparity in incidence. Further investigation in consortial efforts is warranted.     

Racial differences in the association of insulin-like growth factor pathway and colorectal adenoma risk

Purpose

Insulin resistance is believed to play an important role in the link between energy imbalance and colon carcinogenesis. Emerging evidence suggests that there are substantial racial differences in genetic and anthropometric influences on insulin-like growth factors (IGFs); however, few studies have examined racial differences in the associations of IGFs and colorectal adenoma, precursor lesions of colon cancer.

Methods

We examined the association of circulating levels of IGF-1, IGFBP-3 and IGFBP-1, and SNPs in the IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and insulin receptor genes with risk of adenomas in a sample of 410 incident adenoma cases and 1,070 controls from the Case Transdisciplinary Research on Energetics and Cancer (TREC) Colon Adenomas Study.

Results

Caucasians have higher IGF-1 levels compared to African Americans; mean IGF-1 levels are 119.0 ng/ml (SD = 40.7) and 109.8 ng/ml (SD = 40.8), respectively, among cases (p = 0.02). Mean IGF-1 levels are also higher in Caucasian controls (122.9 ng/ml, SD = 41.2) versus African American controls (106.9, SD = 41.2), p = 0.001. We observed similar differences in IGFBP3 levels by race. Logistic regression models revealed a statistically significant association of IGF-1 with colorectal adenoma in African Americans only, with adjusted odds ratios (ORs) of 1.68 (95 % CI 1.06–2.68) and 1.68 (95 % CI 1.05–2.71), respectively, for the second and third tertiles as compared to the first tertile. One SNP (rs496601) in IGF1R was associated with adenomas in Caucasians only; the per allele adjusted OR is 0.73 (95 % CI 0.57–0.93). Similarly, one IGF2R SNP (rs3777404) was statistically significant in Caucasians; adjusted per allele OR is 1.53 (95 % CI 1.10–2.14).

Conclusion

Our results suggest racial differences in the associations of IGF pathway biomarkers and inherited genetic variance in the IGF pathway with risk of adenomas that warrant further study.     

The association between race and prostate cancer risk on initial biopsy in an equal access,multiethnic cohort

Purpose

Population-based studies have established a link between race and prostate cancer (PC) risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. We investigated the association between race and risk of low- and high-grade PC in men undergoing initial prostate biopsy in an equal access medical center.

Methods

We conducted a retrospective record review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs Medical Center who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index, number of cores taken, prostate-specific antigen (PSA), and digital rectal examination findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. ≥7).

Results

Black men were younger at biopsy (61 vs. 65 years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001). A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In multivariable analyses, black race was significantly predictive of PC overall [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p = 0.139).

Conclusion

In an equal access healthcare facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade PC after adjusting for clinical characteristics. Additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.     

Paclitaxel plus platinum or gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer: results from 6 randomized controlled trials

Aim

The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis.

Methods

An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg’s funnel plot and Egger’s test using Stata/SE version 10.1 software.

Results

Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88–1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90–1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90–1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00–1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97–1.14, p = 0.20). Grade 3–4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35–0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30–0.45, p < 0.00001; RR = 0.20, 95 % CI = 0.14–0.27, p < 0.00001; respectively). Grade 3–4 sensory neuropathy, fatigue and neutropenia were comparable between the two groups. Sensitivity analyses in studies of paclitaxel compared with gemcitabine combined with the same platinum strengthened the above conclusion.

Conclusions

Our meta-analysis showed that paclitaxel plus platinum had similar efficacy and less toxicity compared with gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer.     

Understanding disparities in leukemia: a national study

Purpose

Disparities in solid tumors have been well studied. However, disparities in hematologic malignancies have been relatively unexplored on population-based levels. The purpose of this study is to examine the relationship between race/ethnicity and acute leukemia mortality.

Methods

All patients with acute leukemia [acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML)] were identified in the Surveillance Epidemiology and End Results database, 1999–2008. Kaplan–Meier curves were generated to reflect survival probabilities by race/ethnicity. Multivariable Cox proportional hazard models estimated hazard of mortality by race with adjustment for individual (age, gender, year of diagnosis) and select genetic factors.

Results

A total of 39,002 patients with acute leukemia were included in the study. Overall, there was a mortality disparity in acute leukemia for blacks (HR 1.17, p?<?0.0001) and Hispanics (HR 1.13, p?<?0.0001) compared with non-Hispanic whites. In stratified analysis, disparities in ALL were greater than AML; blacks (HR[ALL]1.45, p?<?0.0001; HR[AML]1.12, p?<?0.0011); Hispanics (HR[ALL]1.46, p?<?0.0001; HR[AML]1.06, p?<?0.0001). Adjustment for individual patient and select genetic factors did not explain disparities.

Conclusions

Blacks and Hispanics suffer decreased survival in acute leukemia as compared to others. Further investigation is needed to understand the drivers of poor cancer outcomes in these populations.     

Polymorphisms in HIF-1alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx

Background

HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression.

Methods

We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR–RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables.

Results

Advanced tumors (T3–T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032).

Conclusions

The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size.     

Pharmacodynamic stimulation of thrombogenesis by angiotensin (1–7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy

Purpose

This randomized, double-blind, placebo-controlled Phase 2 study evaluated safety and efficacy of A(1–7) for reduction in Grade 3–4 thrombocytopenia in patients receiving myelosuppressive chemotherapy. Pharmacodynamic activity of A(1–7) in platelet production and retention of scheduled dose intensity were also determined.

Methods

Thirty-four patients with ovarian, Fallopian tube, or peritoneal carcinoma receiving gemcitabine and carboplatin or cisplatin were evaluated. Patients were randomized to receive study drug subcutaneously at 100 mcg/kg (n = 11), 300 mcg/kg (n = 13), or placebo (n = 10) following chemotherapy for up to six cycles. Hematologic variables were obtained throughout each treatment cycle.

Results

There were no drug-related safety issues. There were no instances of Grade 4 thrombocytopenia in patients who received 100 mcg/kg treatment compared to 6 % of chemotherapy cycles for patients receiving placebo (p = 0.07). The maximal percentage increase in platelet concentration from baseline was higher for patients who received 100 mcg/kg A(1–7) compared to placebo (p = 0.02). This increase was accompanied by a reduction in the nadir absolute neutrophil count (p = 0.04). Relative dose intensity for the combination chemotherapy was higher for patients who received 100 mcg/kg A(1–7) compared to placebo (p = 0.04). There were no differences in outcomes for patients receiving 300 mcg/kg dose compared to placebo.

Conclusions

A 100 mcg/kg dose of A(1–7) was shown to produce pharmacodynamic effects on peripheral blood platelet counts, preserve planned dose intensity, and reduce Grade 3–4 thrombocytopenia following gemcitabine and platinum chemotherapy. These findings are consistent with A(1–7)-induced stimulation of thrombogenesis in the bone marrow following marrow-toxic chemotherapy.     

Is extracapsular tumour spread a prognostic factor in patients with early breast cancer?

Background

This study searched for extra capsular tumour spread (ECS) as a prognostic factor for recurrence in terms of Disease Free Survival (DFS) and Overall Survival (OS).

Patients and methods

For this study, from a retrospective database of the Doubs cancer registry, 823 eligible women with node positive breast cancer treated from February 1984 to November 2000 were identified. The following factors were evaluated: ECS, numbers of involved nodes, histological tumour grade, tumour size, status of estrogen and progesterone receptors, and age of patient. A Cox proportional hazards method was used to search for significant factors related to OS and DFS length.

Results

In the multivariate analysis, factors related to DFS length were found to be: tumour grade (aHR 0.76, 95 % CI 0.61–0.96, p = 0.02), ECS status (aHR 0.7, 95 % CI 0.49–0.96, p = 0.03), progesterone (PgR) status (aHR 0.63, 95 % CI 0.44–0.85 p = 0.008), number of nodes involved (aHR 0.75, 95 % CI 0.56–1, p = 0.05). The multivariate analysis for OS found as significant factors: tumour grade (aHR 0.76, 95 % CI 0.61–0.95; p = 0.02) and PgR status (aHR 0.8, 95 % CI 0.56–0.99, p = 0.02).

Conclusions

This study might suggest taking into account ECS status in the adjuvant decision-making process.     

The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme

Background and aims

Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols.

Methods

Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23–81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures.

Results

Compared with c-Met? subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2–1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1–2.3, p < 0.05).

Conclusions

Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.