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  • Hemminki, Kari, et al. (författare)
  • Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?
  • 2012
  • Ingår i: Annals of Oncology. - Oxford University Press. - 1569-8041. ; 23:10, s. 2720-2724
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is diagnosed at the metastatic stage. We aimed to identify hidden primary cancers in CUP patients by comparison with cancers in family members. We take use of the fact that the cause of death in CUP patients is often coded as the cancer in the organ of fatal metastasis. Forty-one thousand five hundred and twenty-three CUP patients were identified in the Swedish Family-Cancer Database, and relative risks (RRs) were calculated for cancer in offspring when family members were diagnosed with CUP and died of the cancer diagnosed in offspring. The RR for lung cancer in offspring was 1.85 when a family member was diagnosed with CUP and died of lung cancer. Significant familial associations were found for seven other cancers. Many familial associations were also significant when offspring CUP patients died of the cancer diagnosed in family members. The cause of death after CUP diagnosis frequently matched the cancer found in a family member, suggesting that the CUP had originated in that tissue. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These novel data suggest that some CUP cases are phenotypically modified primary cancers rather than cancers of unknown primaries.
  • Hemminki, Kari, et al. (författare)
  • Site-specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries.
  • 2012
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136.
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary site (CUP) is a fatal cancer ranking among the five most common cancer deaths. CUP is diagnosed through metastases, which are limited to lymph nodes in some patients. Cause-specific survival data could guide the search for hidden primary tumors and help with therapeutic choices. The CUP patients were identified from the Swedish Cancer Registry between 1987 and 2008; 1444 patients had only lymph node metastasis of defined histology (adenocarcinoma, squamous cell or undifferentiated). Site-specific cancer deaths were analyzed by lymph node location and histology. Kaplan-Meier survival curves were compared with metastatic primary cancer at related sites. Among the patients with metastasis to head and neck lymph nodes, 117 (59.1% of the specific cancer deaths) died of lung tumors. Patients with axillary lymph node metastasis died of lung and breast tumors in equal proportions (40.2% each). Also, squamous cell CUP in head and neck lymph nodes was mainly associated with lung tumor deaths (53.1%). With a few exceptions, survival of CUP patients with lymph node metastasis was indistinguishable from survival of patients with metastatic primary cancer originating from the organs drained by those nodes. The association between lymph node CUP metastases with cancer deaths in the drained organ and the superimposable survival kinetics suggests that drained organs host hidden primaries. Importantly, half of all site-specific cancer deaths (266/530) were due to lung tumors. Thus, an intense search should be mounted to find lung cancer in CUP patients with lymph node metastases.© 2012 Wiley Periodicals, Inc.
  • Hemminki, Kari, et al. (författare)
  • Site-specific survival rates for cancer of unknown primary (CUP) according to location of metastases.
  • 2013
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 133:1, s. 182-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is diagnosed at the metastatic stage and despite extensive diagnostic work-up the primary tumor often remains unidentified. Limited population-based survival data are available for metastatic location and none are available that link the location with the cause of death, which might give clues about the tissue of origin. A total of 9,306 CUP patients with extranodal metastases of adenocarcinoma and undifferentiated histology were identified from the Swedish Cancer Registry. Hazard ratios (HRs), mean survival times and Kaplan-Meier survival curves were provided according to CUP location at diagnosis and cause of death. The median survival was shortest (2 months) for patients with liver and longest (5 months) for those with nervous system metastases. Lung cancer was the most common cause of death in patients with CUP metastasis in the respiratory system, nervous system, bone and skin, with a median survival of 3 months. Patients with peritoneal/retroperitoneal and pelvical metastasis died of ovarian cancer, with a favorable median survival of 8 months, but also of pancreatic and colorectal cancers. Patients with pancreatic, liver, biliary and colorectal cancers with liver metastasis succumbed quickly. The data show that the location of metastases predicts site-specific cancer deaths which in turn may point to the hidden primary tumor. The results should facilitate the management of CUP in proposing that the diagnostic arsenal should target the lungs when metastases are diagnosed in the respiratory or nervous system, bone or skin; ovarian tumors should be suspected after diagnosis of pelvical metastases. © 2012 Wiley Periodicals, Inc.
  • Hemminki, Kari, et al. (författare)
  • Survival in cancer of unknown primary site: population-based analysis by site and histology
  • 2012
  • Ingår i: Annals of Oncology. - Oxford University Press. - 1569-8041. ; 23:7, s. 1854-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer of unknown primary (CUP) is diagnosed at a metastatic stage, conferring an unfavorable prognosis. The natural history of the disease is poorly understood, which complicates diagnosis, treatment and follow-up. Population-based survival data are lacking regarding location and histology of metastases. From the Swedish Cancer Registry, 18 911 CUP patients were identified between years 1987 and 2008. Survival was analyzed by Kaplan-Meier survival curves and Cox regression. Adenocarcinoma accounted for 70% of all extranodal cases with a 12-month survival of 17% and the median survival of 3 months. Adenocarcinoma was also the most common histology (33.4%) when metastases were limited to lymph nodes, with a 12-month survival of 41% and median survival of 8 months. For extranodal metastases, the extremes in survival were small intestinal cancer with poor prognosis and mediastinal cancer with favorable prognosis. For nodal metastases, patients affected in the head and neck, axillary and inguinal regions had the best prognosis and those with abdominal and intrapelvic metastases the worst prognosis. The present data underline the importance of histology and location of metastasis in assisting clinical decision making: hazard ratios differed by a factor of five among extranodal and nodal metastases.
  • Hemminki, Kari, et al. (författare)
  • The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution.
  • 2010
  • Ingår i: Journal of Autoimmunity. - Elsevier. - 0896-8411. ; 34, s. 307-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous family and twin studies have indicated that Graves' disease has a heritable component. Family studies have also shown that some autoimmune disease cluster in families and genetic studies have been able to show shared susceptibility genes. In the present nation-wide study we describe familial risk for Graves' disease among parents and offspring, singleton siblings, twins and spouses with regard to age of onset, gender and number and type of affected family members. Additionally familial association of Graves' disease with any of 33 other autoimmune and related conditions was analyzed. The Swedish Multigeneration Register on 0-75-year-old subjects was linked to the Hospital Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for Graves' disease compared to those whose relatives were unaffected. The total number of hospitalized Graves' patients was 15,743. Offspring with an affected family member constituted 3.6% of all patients among offspring. The familial SIR was 5.04 for individuals whose sibling was affected but it increased to 310 when two or more siblings were affected; the SIR in twins was 16.45. Familial risks were higher for males than for females. The SIR was increased to 6.22 or 30.20 when parental age was limited to 50 or 20 years, respectively. Graves' disease associated with 19 other autoimmune and related conditions, including Addison's disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia, polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and localized scleroderma. Remarkably, there was a high disease concordance of 2.75 between spouses. The clustering between spouses suggests environmental effects on Graves' disease which may contribute to the observed gender effects. The demonstrated high risks should be considered in clinical counseling and in prevention plans.
  • Riihimäki, Matias, et al. (författare)
  • Causes of death in patients with extranodal cancer of unknown primary: searching for the primary site
  • 2014
  • Ingår i: BMC Cancer. - BioMed Central. - 1471-2407. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer of unknown primary (CUP) is a fatal cancer, accounting for 3-5% of all diagnosed cancers. Finding the primary site is important for therapeutic choices and we believe that the organ which is designated as the cause of death may give clues about the primary site. Methods: A total of 20,570 patients with CUP were identified from the Swedish Family-Cancer Database. Causes of death - as reported in the death certificate - were investigated, analyzing reported metastatic sites and histological subtypes separately. Survival was compared with metastatic cancer with a known primary tumor. Results: An organ-specific cancer could be identified as a cause of death in approximately 60% of all CUP patients with adenocarcinoma or undifferentiated histology. In adenocarcinoma, lung cancer was the most frequent cause of death (20%), followed by pancreatic cancer (14%), and ovarian cancer (11%). Lung cancer was the most common cause of death in patients with CUP metastases diagnosed in the nervous system (69%), respiratory system (53%), and bone (47%), whereas ovarian cancer was the most common cause of death when CUP was diagnosed in the pelvis (47%) or the peritoneum (32%). In CUP diagnosed in the liver, liver and pancreatic cancers accounted for 26% and 22% of deaths, respectively. Also in squamous cell CUP, lung cancer was the most common cause of death (45%). Conclusions: According to the causes of death, the primary site appeared frequently to be either the organ where CUP metastases were diagnosed or an organ which may be traced through the known metastatic patterns of different cancer types.
  • Riihimäki, Matias, et al. (författare)
  • Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer
  • 2013
  • Ingår i: BMC Cancer. - BioMed Central (BMC). - 1471-2407. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer of unknown primary site (CUP) is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods: 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs) of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Results: Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66-0.72]). The exceptions were cancer of the pancreas (1.71 [1.54-1.90]), liver (1.58 [1.36-1.85]), and stomach (1.16 [1.02-1.31]). For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06-1.46]). The median survival time of CUP patients was three months. Conclusions: Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the metastatic process at the population level demonstrated large survival differences in organ defined metastases depending on the original cancer.
  • Riihimäki, Matias, et al. (författare)
  • Metastatic sites and survival in lung cancer.
  • 2014
  • Ingår i: Lung Cancer. - Elsevier. - 1872-8332. ; 86:1, s. 78-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Population-based data on metastatic sites and survival in site-specific metastases are lacking for lung cancer and for any cancer because most cancer registries do not record metastases. This study uses a novel population-based approach to identify metastases from both death certificates and national inpatient data to describe metastatic pathways in lung cancer patients.
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