Disparate survival trends in histologic subtypes of metastatic non-small cell lung cancer: a population-based analysis

Erlotinib, bevacizumab, and pemetrexed improved survival of metastatic non-small cell lung cancer (mNSCLC) in clinical trials, but their benefits are restricted to non-squamous histology. We studied recent survival trends in mNSCLC subpopulations defined by histology and associated clinical factors correlating with adenocarcinoma or endothelial growth factor receptor mutations. Using the Surveillance, Epidemiology and End Results database, we calculated relative survival at 1 year from diagnosis for mNSCLC cases diagnosed in 2000-2011. Trends by histology, age, sex, race, prevalence of smoking or poverty, expressed as annual percent change (APC) using joinpoint regression, were compared by test of slope parallelism (P_par). Among 226,446 cases, 47% had adenocarcinoma, 20% squamous carcinoma, 6% other, and 27% unspecified histology. The proportion of cases designated as adenocarcinoma significantly increased after 2005. One-year survival increased from 23.5% in 2000 to 30.5% in 2010, significantly more for adenocarcinoma (APC, 3.3%) than squamous carcinoma (APC, 2.1%, P_par=0.0018). For patients with adenocarcinoma, these trends were significantly better for Asians than Whites (P_par=0.012) and for areas with fewer smokers (P_par=0.014). Such differences were not observed for squamous carcinoma (P_par=0.87 and 0.14, respectively). The absolute disparity in one-year survival between adenocarcinoma and squamous carcinoma increased from 1.6% in 2000 to 5.5% in 2010. The disparity between Asians and Whites increased from 5.2% to 13.1%, respectively. These data demonstrate that improvement in survival of mNSCLC since 2000 is now evident on a population scale. The superior increment for patients with adenocarcinoma, particularly among Asians and in communities with fewer smokers, suggests impact of the newly introduced, histology-specific agents, rather than better supportive care alone. Growing disparities between adenocarcinoma and squamous carcinoma highlight the needs to intensify research on treatment for subgroups that did not benefit from recent advances.     

Declining lung cancer rates among young men and women in the United States: a cohort analysis

Although overall age-adjusted rates of mortality from lung cancer in the United States continue to rise, rates at ages below 45 years have begun to decline. In this report we show that the decrease is greatest among white men, with a 29% drop between the mid-1970s and mid-1980s, but a decrease also occurred among black men and white and black women. Cohort analyses revealed that the rates of lung cancer peaked among men born around 1925-1930 and among women born around 1935-1940, and have declined thereafter. If these trends continue, overall lung cancer mortality rates will start to decline in the 1990s among men and after the year 2000 among women.     

The survival of esophageal cancer by subtype in China with comparison to the United States

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the main subtypes of esophageal cancer (EC), but nationwide survival of both EC subtypes has never been reported in China. Our study aimed to estimate the survival trends of EC by subtype in China and compare them with those in the United States for the same period. We used data from 64 Chinese cancer registries, which included EC patients diagnosed during 2008 and 2015 and followed up until 31st December 2017. The 5-year age-standardized relative survival by subtype, sex, age group and urban or rural area between 2008 and 2017 were analyzed. We stratified survival estimates by calendar period (2008-2009, 2010-2011, 2012-2014 and 2015-2017). Data from the SEER 18 program were calculated to estimate the survival of EC in the United States. A further comparison between the survivals in areas covered and not covered by population-based endoscopic screening programs in China was conducted. A total of 129 962 records were included in the survival analyses. Results revealed that age-standardized 5-year relative survivals for AC and SCC increased in both China and the United States from 2008 to 2017. In 2015 to 2017, 5-year survival from both subtypes in China was better than the United States (SCC: 36.9% vs 18.5%, AC: 34.8% vs 22.3%). The survival for both subtypes was significantly higher in screening areas than in nonscreening areas in China (SCC: 40.6% vs 32.8%; AC: 43.0% vs 31.3%). A survival gap in EC by subtype exists between China and the United States. Our results may support the beneficial effect of population-based endoscopic screening for survival, and may be poised to inform national policy-making in both countries.     

Effect of histologic subtype on treatment and outcomes for esophageal cancer in the United States

BACKGROUND:

Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct clinico‐pathologic characteristics; however, it is unclear whether treatment patterns differ by histologic subtype. The objective of this study was to examine differences in treatment use and outcomes by histologic subtype for esophageal cancer in the United States.

METHODS:

From the National Cancer Data Base, patients with esophageal cancer were identified. Regression models were formulated to assess the influence of histologic subtype on treatment use and overall survival.

RESULTS:

From 1998 to 2007, 80,961 patients were identified with esophageal cancer in the United States. A higher percentage of patients with nonmetastatic AC underwent surgical resection compared with patients with nonmetastatic SCC (AC, 65.7%; SCC, 36.0%; P<.001), who were more often treated with chemoradiotherapy alone (AC, 25.7%; SCC, 54.1%; P<.001). High‐volume academic centers used surgery more frequently for both AC and SCC than did other centers, yet even at high‐volume academic centers, surgery was used much less often to treat SCC than AC (AC, 79.3%; SCC, 53.7%; P<.001). The likelihood of operative treatment for nonmetastatic disease was significantly lower in patients with SCC compared with patients with AC (P<.001). Overall survival was lower for patients with stage II/III disease of either histologic subtype treated with chemoradiotherapy alone compared with surgery plus chemoradiotherapy (P<.001).

CONCLUSION:

A large proportion of patients with esophageal cancer are being treated nonoperatively, and treatment use varies according to tumor histology, particularly by center type. Cancer 2011. © 2011 American Cancer Society.     

Lung cancer mortality trends in 36 European countries: secular trends and birth cohort patterns by sex and region 1970–2007

Smoking is a major contributor to all‐cause mortality in Europe and accounts for one‐fifth of the cancer‐related deaths. Monitoring the tobacco epidemic via an analysis of lung cancer trends is essential in helping countries arrest the effects of tobacco epidemic in the region. The study aims to provide a comprehensive and up‐to‐date overview of the temporal patterns of lung cancer mortality in Europe, emphasizing country‐ and sex‐specific differences. National lung cancer mortality data were extracted from the WHO mortality databank by age, sex, year of death (1970–2007) for 36 countries in Europe. Trends in lung cancer mortality in men have tended to decrease in many European countries during the last two decades, particularly in North and Western Europe. Among women, mortality rates are still increasing in many countries, although in a few populations, rates are beginning to stabilize, notably in the high‐risk countries within Eastern Europe (Hungary, Poland and the Czech Republic), and in Northern Europe (Denmark, Iceland and the United Kingdom). Men and women are clearly in very different phases of the smoking epidemic, and, as reflected in the mortality rates by birth cohort, the stage varies widely by country within each European region. That lung cancer mortality trends in men are on a downwards path in most European countries while female rates continue to rise, points to an urgent need for national and European prevention strategies that target tobacco cessation and prevention among European women.     

Flavonoid consumption and esophageal cancer among black and white men in the United States

Flavonoids and proanthocyanidins are bioactive polyphenolic components of fruits and vegetables that may account for part of the protective effect of raw fruit and vegetable consumption in esophageal cancer. We studied the relationship between esophageal cancer and dietary proanthocyanidins, flavonoids and flavonoid subclasses (anthocyanidins, flavan‐3‐ols, flavanones, flavones, flavonols and isoflavonoids) using recently developed USDA and Tufts flavonoid and proanthocyanidin databases. The study was a population‐based, case–control analysis of 161 white men with esophageal adenocarcinoma (EAC), 114 white and 218 black men with esophageal squamous cell carcinoma (ESCC) and 678 white and 557 black male controls who lived in 3 areas of the United States. Neither total flavonoid nor proanthocyanidin intake was associated with EAC and ESCC in either white or black men. In white men, inverse associations were observed between anthocyanidin intake and EAC (4th vs. 1st quartile odds ratio [OR], 0.47, 95% confidence interval [CI], 0.24–0.91; p_trend = 0.04) and between isoflavonoid intake and ESCC (4th vs. 1st quartile OR, 0.43, 95% CI, 0.20–0.93; p_trend = 0.01). None of the associations remained significant after adjusting for dietary fiber, which is strongly correlated with flavonoid consumption. We conclude that total flavonoids and proanthocyanidins do not have strong protective effects in either EAC or ESCC. Some protective effects were evident in flavonoid subclasses and population subgroups. In white men, foods rich in anthocyanidins may have chemopreventive effects in EAC and those rich in isoflavonoids may do so in ESCC. © 2009 UICC     

4种肿瘤标志物在肺癌病理分型、分期中的临床价值

目的：探讨CEA、SCC-Ag、NSE、CA125与肺癌病理分型以及临床特征之间的关系。方法：应用电化学发光方法检测109例肺癌患者血清中4种肿瘤标志物水平。结果：CEA在腺癌中的水平明显高于其他类型的肺癌（P＝0．003）;SCC-Ag在鳞癌中的水平明显高于其他类型的肺癌（P＝0．006）;NSE 在小细胞肺癌中的水平明显高于其他类型的肺癌（P＝0．001）。CEA在T3、T4分期表达的水平明显高于T1和T2分期（P＝0．041）。NSE和CA125在N2和N3期患者中表达水平明显高于N0和N1期患者（P＜0．05）。CEA在有远处转移的患者中表达水平明显高于无转移的患者（P＝0．038）。CEA和SCC-Ag转移部位越多,其表达越高（P＜0．05）。CEA在Ⅳb 期患者中表达水平明显高于Ⅰ＋Ⅱ＋Ⅲ和Ⅳa 期患者（P＝0．037）。CA125在有胸腔积液的患者中表达水平明显高于无胸腔积液的患者（P＝0．001）。结论：CEA对晚期腺癌的诊断价值较高, SCC-Ag是诊断鳞癌有价值的标志物,NSE对小细胞肺癌有较高的诊断价值。CEA与临床分期正相关,高表达预示分期晚,低表达则对分期参考作用小。CEA及SCC-Ag高浓度应高度警惕有无多部位转移,CA125水平高提示可能存在胸膜转移。     

Global patterns and trends in stomach cancer incidence: Age,period and birth cohort analysis

The cases of stomach cancer (SC) incidence are increasing per year and the SC burden has remained very high in some countries. We aimed to evaluate the global geographical variation in SC incidence and temporal trends from 1978 to 2007, with an emphasis on the effect of birth cohort. Joinpoint regression and age–period–cohort model were applied. From 2003 to 2007, male rate were 1.5‐ to 3‐fold higher than female in all countries. Rates were highest in Eastern Asian and South American countries. Except for Uganda, all countries showed favorable trends. Pronounced cohort‐specific increases in risk for recent birth cohorts were seen in Brazil, Colombia, Iceland, New Zealand, Norway, Uganda and US white people for males and in Australia, Brazil, Colombia, Costa Rica, Czech Republic, Ecuador, Iceland, India, Malta, New Zealand, Norway, Switzerland, United Kingdom, Uganda, US black and white people for females. The cohort‐specific ratio for male significantly decreased in Japan, Malta and Spain for cohorts born since 1950 and in Austria, China, Croatia, Ecuador, Russia, Switzerland and Thailand for cohorts born since 1960 and for female in Japan for cohorts born since 1950 and in Canada, China, Croatia, Latvia, Russia and Thailand for cohorts born since 1960. Disparities in incidence and carcinogenic risk persist worldwide. The favorable trends may be due to changes in environmental exposure and lifestyle, including decreased Helicobacter pylori prevalence, increased intake of fresh fruits and vegetables, the availability of refrigeration and decreased intake of salted and preserved food and smoking prevalence.     

Lung cancer incidence in young women vs. young men: A systematic analysis in 40 countries

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5-year age group (ages 30–64) and 5-year calendar period (1993–2012) were extracted from Cancer Incidence in Five Continents. Female-to-male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age-specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female-to-male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45–49 year in the Netherlands increased from 0.7 (95% CI: 0.6–0.8) to 1.5 (95% CI: 1.4–1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.     

Niacin intake and risk of skin cancer in US women and men

A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984–2010) and 41,808 men in the Health Professionals Follow‐up Study (1986–2010). Niacin intake was assessed every 2 to 4 years during follow‐up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort‐specific results were pooled using a random‐effects model. During the follow‐up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74–0.95; p_trend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01–1.10; p_trend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.     

Incidence and survival rate of women with cervical cancer in the Greater Amsterdam area

To evaluate the effect of population-based cervical cancer screening on the occurrence of cervical cancer in The Netherlands, we investigated the incidence and survival of cervical cancer registered by a cancer registry in the Greater Amsterdam area. The incidence rate of squamous cell carcinoma decreased significantly from 9.2/100,000 women in 1988 to 5.9/100,000 in 2000 (P<0.001). The incidence rate of adenocarcinomas remained stable. After adjustment for age, stage and lymph node involvement, the relative risk of death was 1.6 times higher for patients with adenocarcinomas than for patients with squamous cell carcinoma (95% CI 1.2-2.1). The decreased survival was related to histological type, as the effect remained significant after correction for confounding factors. Over time, the prognosis of women with squamous cell carcinoma improved significantly. No significant change was observed for women diagnosed with adenocarcinoma. These results suggest that the screening programme in The Netherlands as executed in the Greater Amsterdam area is associated with a decreased incidence and increased survival of patients with squamous cell carcinoma, but fails to detect (pre)malignant lesions of adenocarcinoma. Since more than 92% of adenocarcinomas and its precursors contain high-risk HPV, adding HPV testing to cytologic screening might improve the present screening programme in detecting adenocarcinoma and its precursor lesions.     

Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study

Background

Renal-cell carcinoma (RCC) is one of the common malignancies in the United States. RCC incidence and mortality have been changing for many reasons. We performed a thorough investigation of incidence and mortality trends of RCC in the United States using the cell Surveillance, Epidemiology, and End Results (SEER) database.

Testicular cancer: marked birth cohort effects on incidence and a decline in mortality in southern Netherlands since 1970

The aim of our study was to interpret the changing incidence, and to describe the mortality of patients with testicular cancer in the south of the Netherlands between 1970 and 2004. On the basis of data from the Eindhoven Cancer Registry and Statistics Netherlands, 5-year moving average standardised incidence and mortality rates were calculated. An age-period-cohort (APC) Poisson regression analysis was performed to disentangle time and birth cohort effects on incidence. The incidence rate remained stable for all ages at about 3 per 100,000 person-years until 1989 but increased annually thereafter by 4% to 6 in 2004. This increase can almost completely be attributed to an increase in localised tumours. The largest increase was found for seminoma testicular cancer (TC) patients aged 35-39 and non-seminoma TC patients aged 20-24 years. Relatively more localised and tumours with lymph node metastases were detected in the later periods. APC analysis showed the best fit with an age-cohort model. An increase in incidence of TC was found for birth cohorts since 1950. The mortality rate dropped from 1.0 per 100,000 person-years in 1970 to 0.3 in 2005, with a steep annual decline of 12% in the period 1979-1986. In conclusion, the increase in incidence of TC was strongly correlated with birth cohorts since 1945. The increase in incidence is possibly caused by in utero or early life exposure to a yet unknown risk factor. There was a steep decline in mortality in the period 1979-1986.     

NaPi2b expression in a large surgical Non-Small Cell Lung Cancer (NSCLC) cohort

BackgroundNaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumors including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts.MethodsAnalyses were performed on archival formalin fixed paraffin embedded primary tumor specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 – 300) were calculated for each core tissue sample (H-score = % tumor cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive.ResultsOf 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029).ConclusionHigh NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma.     

Cigarette smoking and subsequent risk of lung cancer by histologic type in middle-aged Japanese men and women: the JPHC study

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population-based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non-smokers was 4.5 [95% confidence interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI: 4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI: 0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma.     

Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of United States women

Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer. Thus, the association of fatal breast cancer and spontaneous abortion was examined in a large prospective study of United States adult women. After seven years of follow-up, 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories. Results from Cox proportional hazards models, adjusted for other risk factors, showed no association between a history of spontaneous abortion and risk of fatal breast cancer (rate ratio [RR]=0.89, 95 percent confidence interval [CI]=0.78–1.02). The RR did not increase with increasing numbers of abortions. Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion (RR=0.76, CI=0.54–1.05). Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant (RR=0.61, CI=0.27–1.38) or whose only pregnancy ended in a livebirth (RR=0.72, CI=0.32–1.65). These findings do not support an association between spontaneous abortion and fatal breast cancer.     

Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site-specific cancer incidence in relation to birth characteristics in a Swedish population-based cohort of 11,166 singletons born in 1915-1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow-up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex-adjusted) increases of 13% (95% CI = 0.03-0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01-0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09-0.79), but reduced rates (by 24%; 95% CI = 0.07-0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer.     

Temporal trends in non-small cell lung cancer survival in Sweden

We modeled temporal trends in the 1- and 5-year survival of 32 499 patients with adenocarcinoma and squamous cell carcinoma of the lung in the Swedish Cancer Register between 1961 and 2000. The 1-year relative survival for adenocarcinoma improved from 37% for patients diagnosed 1961-1965 to 45% for those diagnosed 1996-2000 and from 39 to 45% for squamous cell carcinoma. The adjusted excess mortality ratios for the period 1996-2000 compared with 1961-1965 were 0.80 for adenocarcinoma and 0.81 for squamous cell carcinoma. Thus, a previous report in a Dutch study of a relatively worsening prognosis for adenocarcinoma over time could not be confirmed.