Cancer risk of Lichen planus: A cohort study of 13,100 women in Finland

The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population‐based Finnish register data. All women with the diagnosis of LP (n = 13,100) were identified from the Finnish Hospital Discharge Registry from 1969–2012. These patients were linked with subsequent cancer diagnoses from the Finnish Cancer Registry until 2014. Standardized incidence ratios (SIRs) were counted for different cancers by dividing the observed numbers of cancers by expected numbers, which were based on national cancer incidence rates. In total, 1,520 women with LP were diagnosed with cancer (SIR 1.15, 95% confidence interval [CI] 1.09–1.20). LP was associated with an increased risk of cancer of lip (SIR 5.17, 95% CI 3.06–8.16), cancer of tongue (SIR 12.4, 95% CI 9.45–16.0), cancer of oral cavity (SIR 7.97, 95% CI 6.79–9.24), cancer of esophagus (SIR 1.95, 95% CI 1.17–3.04), cancer of larynx (SIR of 3.47, 95% CI 1.13–8.10) and cancer of vulva (SIR 1.99, 95% CI 1.18–3.13). The risk of cancer was not increased in other locations where LP manifests (pharynx and skin). Patients with diagnosed LP have an increased risk of developing cancer of lip, tongue, oral cavity, esophagus, larynx and vulva. These data are important when considering treatment and follow‐up of patients with LP diagnosis.     

Haemochromatosis and gastrointestinal cancer

Iron overload in patients with haemochromatosis is a strong risk factor for liver cancer, but its influence on other gastrointestinal cancer risk is unclear. The aim was to assess the relative risk of luminal gastrointestinal cancer among patients diagnosed with haemochromatosis. This population‐based, nationwide Swedish cohort study included patients with haemochromatosis in Sweden in 1965–2013. The incidence of gastrointestinal cancers was assessed through the Swedish Cancer Registry. The measure of relative risk was the standardised incidence ratio (SIR) with 95% confidence interval (CI), that is, the ratio of the observed number of gastrointestinal cancers in the haemochromatosis cohort divided by the expected number of such cancers, calculated from the entire corresponding background population of Sweden. Among 6,849 patients in the haemochromatosis cohort with up to 48 years of follow‐up, the SIRs were 3‐fold increased for oesophageal squamous cell carcinoma (SIR = 3.2, 95% CI 1.3–6.6; n = 7) and 40% increased for colon adenocarcinoma (SIR = 1.4, 95% CI 1.1–1.9; n = 54). No associations were found between haemochromatosis and the risk of adenocarcinoma of the oesophagus (SIR = 0.5, 95% CI 0.0–2.5; n = 1), stomach (SIR = 0.7, 95% CI 0.3–1.4; n = 8), small bowel (SIR = 1.2, 95% CI 0.0–6.7; n = 1) or rectum (SIR = 1.0, 95% CI 0.6–1.6; n = 21). These findings indicate that haemochromatosis increases the risk of oesophageal squamous cell carcinoma and colon adenocarcinoma, but might not influence the risk of other types of luminal gastrointestinal cancer. These findings should encourage further research examining the role of iron overload in cancer aetiology.     

Cancer incidence among alcoholic liver disease patients in Finland: A retrospective registry study during years 1996–2013

Both alcohol abuse and liver cirrhosis are known risk factors for various cancers. This article was aimed to assess the long‐term risk of malignancies among patients with severe alcoholic liver disease (ALD), i.e., alcoholic liver cirrhosis and alcoholic hepatitis. A cohort of 8,796 male and 3,077 female ALD patients from 1996 to 2012 was identified from the Finnish National Hospital Discharge Register. This nationwide cohort was combined with the data from the Finnish Cancer Registry for incidence of malignancies during the years 1996–2013. The cancer cases diagnosed were compared with the number of cancers in the general population. The number of malignancies in our cohort was 1,052 vs. 368 expected. There was statistically significant excess of cancers of the liver, (standardized incidence ratio [SIR] 59.20; 95% CI 53.11–65.61), pancreas (SIR 3.71; 95% CI 2.72–4.94), pharynx (SIR 9.25; 95% CI 6.05–13.56), mouth (SIR 8.31; 95% CI 4.84–13,29), oesophagus (SIR 7.92; 95% CI 5.49–11.07), tongue (SIR 7,21; 95% CI 3.60–12.89), larynx (SIR 5.20; 95% CI 2.77–8.89), lung (SIR 2.77; 95% CI 2.27–3.32), stomach (SIR 2.76; 95% CI 1.79–4.07), kidney (SIR 2.69; 95% CI 1.84–3.79) and colon (SIR 2.33; 95% CI 1.70–3.11). There was no decreased risk of any cancer among ALD patients. Severe ALD is associated with markedly increased risk of malignancies. The risk is especially high for hepatocellular carcinoma, but also significantly increased for cancers of the upper aerodigestive tract, pancreas and kidneys, and warrants cancer surveillance in selected cases.     

Second cancers following in situ carcinoma of the breast

Carcinoma in situ (CIS) of the breast has increased manyfold in incidence rates and as a proportion of new breast cancers following the introduction of mammographic breast screening. To provide population-based estimates of invasive breast cancer risk following CIS, we linked data on 249 incident primary CIS (median age 53 years) to the Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) over the period 1977–1994. Women with concurrent invasive cancers of the breast were not included. Standardized incidence ratios (SIR) were determined according to the exact Poisson distribution, with stratification for age and year of diagnosis. A total of 24 cases of breast cancer vs. 3.4 expected [SIR = 7.2, 95% confidence interval (CI): 4.6–10.6], and 7 cases of other neoplasms (except non-melanomatous skin cancer) vs. 6.9 expected (SIR = 1.0, 95% CI: 0.4–2.1) were observed. The SIR was 10.4 during the first year, 5.6 between 1 and 4 years, and 7.7 after ≥5 years after CIS diagnosis. SIRs were consistent in women below and above age 55 years, but somewhat higher for ductal (SIR = 8.6) than lobular (SIR = 4.2) CIS. Six deaths from breast cancer were observed vs. 1.5 expected (standardized mortality ratio = 4.0, 95% CI: 1.5–8.7). In 13/19 ductal CIS, but in 2/4 lobular CIS, invasive cancer occurred in the same breast. In most women, CIS and subsequent invasive cancer showed the same morphological (i.e., ductal or lobular) features. The cumulative risk of breast cancer was 16% 10 years after CIS diagnosis, emphasizing the importance of adequate surveillance of women after CIS of the breast. Int. J. Cancer 77:392–395, 1998. © 1998 Wiley-Liss, Inc.     

Immunosuppressive disorders and risk of anal squamous cell carcinoma: A nationwide cohort study in Denmark, 1978–2005

Compromised immune function may increase the risk of anal squamous cell carcinoma (SCC). We examined the risk of anal SCC in patients with HIV infection and other chronic disorders associated with immunosuppression. A population‐based cohort study was conducted using the Danish National Patient Registry and the Danish Cancer Registry (DCR). We identified all patients with a first‐time hospital contact or procedure for HIV infection, solid organ transplantation or autoimmune disease or a first‐time record of haematologic malignancy in the DCR, 1978–2005, and followed these for a subsequent anal SCC, starting follow‐up 1 year after diagnosis of the index disease. Standardised incidence ratios (SIRs) were computed as the ratio of observed to expected numbers of anal SCCs, based on national age‐, sex‐ and period‐specific rates. Among 4,488 patients with HIV, we observed 21 anal SCCs with 0.3 expected (SIR: 81.1 (95% confidence interval (CI): 51.6–121.9)). Risk of anal SCC was markedly increased among 5,113 solid organ recipients (SIR: 14.4 (CI: 7.0–26.4)) and 30,165 patients with haematologic malignancies (SIR: 2.3 (CI: 1.1–4.2)) but only moderately increased among 242,114 patients with autoimmune diseases (SIR: 1.3 (CI: 1.0–1.6)). SIRs varied according to type of autoimmune disease and were high in patients with Crohn's disease (SIR: 3.1 (CI: 1.2–6.4)), psoriasis (SIR: 3.1 (CI: 1.8–5.1)), polyarteritis nodosa (SIR: 8.8 (CI: 1.5–29.0)) and Wegener's granulomatosis (SIR: 12.4 (CI: 2.1–40.8)). In conclusion, we found HIV infection, solid organ transplantation, haematologic malignancies and a range of specific autoimmune diseases strongly associated with increased risk of anal SCC.     

Lichen sclerosus and risk of cancer

Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population‐based Finnish Cancer Registry data to further study this connection. We identified all women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates. During the follow‐up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05–1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9–38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01–9.44). The risk of cancers of the uterine cervix and lung was significantly decreased. LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.     

Risk of virus and non‐virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985–2014

This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person–years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow‐up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8‐fold higher cancer risk (95% CI: 1.6–2.0). SIRs were particularly elevated for virus‐related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0–88.5), non‐Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8–10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1–15.8). Among virus‐unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1–6.2), esophagus (SIR = 6.7, 95% CI: 2.9–13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8–82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0–2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0–5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0–0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients.     

Antiviral therapy improves overall survival in hepatitis C virus‐infected patients who develop diffuse large B‐cell lymphoma

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non‐Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV‐infected patients with diffuse large B‐cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV‐infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004–May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon‐based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first‐line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5‐year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01–5.3]; p = 0.04). Furthermore, AVT improved 5‐year OS rates among cases in both univariate (median [Interquartile range]: 39 [26–56] vs. 16 [6–41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06–0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5‐year OS.     

Cancer risks after solid organ transplantation and after long‐term dialysis

Immunosuppression involves an inability to control virus infections and increased incidence of virus‐associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent. To provide a reliable and generalizable estimate, with high statistical power and long follow‐up time, we assessed cancer risks using comprehensive, population‐based registries in two different countries and from two different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long‐term dialysis patients (LDPs)). National registries in Denmark and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated. We found highly similar results, both for the two different countries and for the two different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non‐melanoma skin cancer (NMSC), non‐Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n = 2,142, 95% CI, 3.4–3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8–3.1] in Denmark and 1.6 [n = 1,713, 95% CI, 1.5–1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n = 994, 95% CI, 42–47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8–45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7–5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression‐related susceptibility to viral infections.     

Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC)

Adding MRI to annual mammography screening improves early breast cancer detection in women with familial risk or BRCA1/2 mutation, but breast cancer specific metastasis free survival (MFS) remains unknown. We compared MFS of patients from the largest prospective MRI Screening Study (MRISC) with 1:1 matched controls. Controls, unscreened if<50 years, and screened with biennial mammography if ≥50 years, were matched on risk category (BRCA1, BRCA2, familial risk), year and age of diagnosis. Of 2,308 MRISC participants, breast cancer was detected in 93 (97 breast cancers), who received MRI <2 years before breast cancer diagnosis; 33 BRCA1 mutation carriers, 18 BRCA2 mutation carriers, and 42 with familial risk. MRISC patients had smaller (87% vs. 52% <T2, p < 0.001), more often node negative (69% vs. 44%, p = 0.001) tumors and received less chemotherapy (39% vs. 77%, p < 0.001) and hormonal therapy (14% vs. 47%, p < 0.001) than controls. Median follow‐up time was 9 years (range 0–14). Breast cancer metastasized in 9% (8/93) of MRISC patients and in 23% (21/93) of controls (p = 0.009). MFS was better in MRISC patients overall (log‐rank p = 0.008, HR 0.36, 95% CI 0.16–0.80), with familial risk (log‐rank p = 0.024, HR: 0.21, 95% CI 0.04–0.95), and in BRCA1 mutation carriers (log‐rank p = 0.055, HR 0.30, 95% CI 0.08–1.13). MFS remained better in MRISC patients after lead time correction (log‐rank p = 0.020, HR 0.40, 95% CI 0.18–0.90). Overall survival was non‐significantly better in MRISC patients (log‐rank p = 0.064, HR 0.51, CI 0.24–1.06). Annual screening with MRI and mammography improves metastasis free survival in women with BRCA1 mutation or familial predisposition.     

The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation

Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan‐Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24‐0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27–1.93; p = 0.52). By subgroup analysis, those younger than 70‐year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04–0.97; p = 0.046). Delayed surgery by 9–12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70‐year old, but further prospectively randomized controlled trials are warranted to validate these findings.     

Overall survival benefits for irinotecan‐containing regimens as first‐line treatment for advanced gastric cancer: An updated meta‐analysis of ten randomized controlled trials

The standard treatment for patients with advanced gastric cancer (AGC) is still debated, and the available data on the benefit of irinotecan‐containing regimen as first‐line treatment for those patients are controversial. We performed a systematic review and meta‐analysis of randomized controlled trials to determine the survival benefits of irinotecan‐containing regimens in this setting. A total of 1,837 patients from ten trials were included in the analysis. Our results showed that irinotecan‐containing regimens significantly improved overall survival [OS: hazard ratio (HR) 0.86, 95% CI = 0.78–0.94, p = 0.002] and progression‐free survival [HR = 0.82, 95% CI = 0.69–0.97, p = 0.026); however, the improvement of time to failure (HR = 0.90; 95% CI = 0.77–1.04, p = 0.15), 1‐year survival rate [1‐year SR: relative risk (RR) 1.10, 95% CI = 0.97–1.24, p = 0.13] and overall response rate (RR = 1.16, 95% CI = 0.91–1.49, p = 0.24] were nonsignificant. Equivalent frequencies of toxicities were found between the two groups excluding more Grade 3 or 4 fatigue (p = 0.001) in irinotecan‐containing regimens. This updated meta‐analysis provided strong evidence for a survival benefit of irinotecan‐containing regimen as first‐line treatment for AGC. A clear advantage of irinotecan‐containing over nonirinotecan‐containing regimen had not been established. These results should help to inform decisions about patient management and design of future trials.     

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence‐free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non‐)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non‐academic hospitals were included. RFS and OS were analyzed with Kaplan‐Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five‐year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68‐1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64–1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three‐year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85–2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70–1.97)). Three‐year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11–3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12–3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.     

Survival in neuroendocrine neoplasms; A report from a large Norwegian population‐based study

Neuroendocrine neoplasms (NENs) are heterogeneous tumors originating from neuroendocrine cells. Their malignant potential varies from indolence to high‐grade malignancy (carcinomas). We studied the survival of all NENs in Norway according to malignant potential and different primary sites. We identified all NEN cases diagnosed in 1993 to 2015 and reported to the national population‐based Cancer Registry of Norway. We included 62 morphological types. According to morphological characteristics and known disease behavior, we stratified the tumors into two different groups: low/intermediate aggressiveness and high aggressiveness. A total of 17,128 NENs were analyzed. Median age was 67 years and 47.6% were females. The most common primary sites were in the lungs and the gastroenteropancreatic (GEP) system. The 5‐year relative survival in patients with low/intermediate aggressive NENs was 64.8% (95% CI, 63.3–66.2) and high aggressive NENs 8.4% (95% CI, 7.8–9.1). Females had higher survival rates than males (p <0.001). The relative 5‐year survival rate in patients younger than 50 years was 89.1% (95% CI, 87.4–90.7) vs 41.0% (95% CI, 34.9–46.9) in patients ≥80 years. In multivariable analysis gender, age at diagnosis, time of diagnosis, stage and primary sites were all predictors of outcome both in patients with low/intermediate tumors and high aggressive tumors. Survival improved significantly over time, regardless of sex, age and tumor stage.     

Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: A meta‐analysis of randomized controlled trials

Available literature on the benefit of interferon alpha (IFN‐α) as adjuvant postsurgical or ablative treatment of hepatocellular carcinoma reports discordant results. By meta‐analysis of the available data, we evaluated the effects of IFN‐α on recurrence and survival after complete resection or ablation of hepatocellular carcinoma. All randomized controlled trials comparing IFN‐α with placebo or no treatment after tumor resection or ablation were selected. Finally, 6 studies published in 2001 or later with a total of 600 patients were included in this meta‐analysis. Data on postsurgical or ablative early recurrence and 1 year survival of hepatocellular carcinoma in IFN‐α treated and untreated patients were extracted from each study. Proportions were combined, and the odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Analysis results show that IFN‐α significantly decreased postsurgical or ablative overall early recurrence (OR = 0.62; 95% CI = 0.42–0.93; p = 0.02) and improved overall 1 year survival (OR = 3.14; 95% CI = 1.79–5.52; p < 0.0001). Subgroup analyses show that IFN‐α decreased postsurgical early recurrence (OR = 0.58; 95% CI = 0.37–0.91; p = 0.02) and improved 1 year survival (OR = 3.19; 95% CI = 1.80–5.67; p < 0.0001) evidently. Subgroup analyses also show that IFN‐α reduced early recurrence after resection without pre‐resection ablation therapy (OR = 0.58; 95% CI = 0.37–0.91; p = 0.02) and improved 1 year survival (OR = 3.83; 95% CI = 2.01–7.27; p < 0.0001). These results suggest that IFN‐α treatment could significantly decrease early recurrence and improve 1 year survival of patients with hepatocellular carcinoma after complete resection or ablation. The use of IFN‐α as adjuvant postsurgical or ablative treatment seems promising but requires further study. © 2009 UICC     

Melanoma incidence trends and survival in adolescents and young adults in Queensland,Australia

Cutaneous melanoma is a relatively common cancer in adolescents and young adults in Australia, but detailed information about occurrence patterns and prognosis is limited. We evaluated incidence trends from 1982 to 2010 and recent survival rates in those aged 15–24 years in the state of Queensland. In situ and invasive melanoma cases were identified from the Queensland Cancer Registry. Incidence rates were age‐standardised to the 2000 World population and trends calculated using joinpoint regression. Five‐year relative survival was estimated by the period method and Poisson models were used to produce adjusted mortality hazard ratios. Average annual incidence rates for the 5‐year period 2006–2010 were 6.3 per 100,000 [95% confidence interval (CI) 5.4, 7.2] for in situ and 10.1 per 100,000 (95% CI 9.0, 11.3) for invasive melanoma. Since the mid‐1990s, incidence rates for in situ melanomas have been stabilizing while invasive melanoma has decreased in both sexes, mainly owing to declining rates of thin tumours (≤1 mm) (?5.4% per year, 95% CI ?8.3%, ?2.4%). Incidence rates of melanomas >1 mm in thickness have remained relatively unchanged since 1991 however. In the period 2006–2010, relative 5‐year survival of 15–24 year olds with invasive melanoma was 95.7% (95% CI 92.9%, 97.5%). The subgroup with tumours >1 mm was nearly six times more likely to die within 5 years than those with thin tumours (adjusted hazard ratio = 5.53, 95% CI 1.72, 17.80). Incidence of thin melanoma in young people in Queensland is declining, suggesting benefits of primary prevention efforts are being realised.     

Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study

The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic‐ and Cox‐regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR) = 0.54 (95% confidence interval (CI):0.40–0.70, p < 0.001). The association only applied to confined hepatic metastases (aOR = 0.30, 95%CI: 0.18–0.49, p < 0.001), whereas the presence of confined pulmonary metastases (aOR = 0.71, 95% CI: 0.39–1.29, p = 0.258) or synchronous hepatic and pulmonary metastases (aOR = 0.69, 95% CI:0.26–1.29, p = 0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR) = 0.76, 95% CI: 0.54–1.06, p = 0.101; Proportional excess hazards: aHR = 0.73, 95% CI: 0.50–1.07, p = 0.111) when adjusting for other prognostic factors. The metastatic pattern varied according to MMR status. MMR had no impact on survival in patients with UICC Stage IV CRC. These findings may be important for the understanding of the metastatic processes and thus for optimizing staging and treatment in CRC patients.     

Acromegaly and cancer risk: a cohort study in Sweden and Denmark

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977–1993; Sweden 1965–1993) were linked to tumor registry data for up to 15–28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5, 95% CI = 1.3–1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.6–2.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2–17.4), colon (SIR = 2.6, 95% CI = 1.6–3.8), and rectum (SIR = 2.5, 95% CI = 1.3–4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI = 1.2–5.0), thyroid (SIR = 3.7, 95% CI = 1.8–10.9), kidney (SIR = 3.2, 95% CI = 1.6–5.5), and bone (SIR = 13.8, 95% CI = 1.7–50.0). Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-1 system in the etiology of various cancers.     

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre‐existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all‐cause and 678 CRC‐specific deaths after a mean follow‐up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC‐specific and all‐cause survival while adjusting for known confounders. Overall, CRC‐specific survival was not associated with pre‐existing T2D (HR = 0.84; 95% CI = 0.67–1.07). However, a significant interaction was seen for comorbidity (p_interaction = 0.03) with better survival among those without pre‐existing conditions (HR = 0.49; 95% CI = 0.25–0.96) while no association was seen in patients with comorbid conditions. All‐cause mortality was also not related to pre‐existing T2D (HR = 1.11; 95% CI = 0.98–1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19–1.56). Stratification by T2D duration suggested higher CRC‐specific and all‐cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre‐existing T2D had no influence on disease‐specific and all‐cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.     

Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study

Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40–60% within 4–12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986–1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp–, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow‐up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow‐up years was 1.62 but decreased from the sixth follow‐up year thereon to 0.14 (CI: 0.00–0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02–1.00, p = 0.049). The SIR for Hp– was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow‐up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp– patients.