Risk of second primary malignancies and causes of death in patients with adenocarcinoma and carcinoid of the small intestine

We studied risk of second malignancies and causes of death in 1829 cases of adenocarcinoma and 3055 cases of carcinoid tumours in the small bowel reported to the Swedish Cancer Registry from 1960 through to 2000. Data on causes of death were analysed as from 1966 whereas data on second tumours was available during the whole registry-period. Follow-up was available until 2001. Standard mortality ratio (SMR) and standard incidence ratio (SIR) were calculated. Female patients with adenocarcinoma had increased risk of acquiring cancer in the female genital organs (SIR 3.2; 95% confidence intervals (CI) 1.9-5.0) and breasts (SIR 2.7; 95% CI 1.1-5.4). Both sexes combined had increased risk of second tumours in the gastrointestinal tract (SIR 1.5; 95% CI 1.1-2.1) and skin (SIR 4.6; 95% CI 1.2-12). Men with carcinoid tumour had increased risk of prostate cancer (SIR 2.8; 95% CI 1.6-4.6). Increased risk was seen for both sexes with carcinoid for malignant melanoma (SIR 6.3; 95% CI 2.7-12), malignant skin tumours (SIR 3.6; 95% CI 1.7-6.7) and malignancies of endocrine organs (SIR 2.3 95% CI 1.3-3.8). Patients with adenocarcinoma had increased risk of dying from malignant diseases other than the primary cancer (SMR 9.5; 95% CI 8.6-10) and gastrointestinal disease (SMR 2.6 95% CI 1.6-4.2). The cohort with carcinoid had higher than expected risk of dying from malignant disease (SMR 4.3; 95% CI 4.0-4.6), gastrointestinal disease (SMR 2.8; 95% CI 2.1-3.6) and cardiovascular disease (SMR 1.1; 95% CI 1.0-1.3). The increased risk of second malignant tumours is an indication of common aetiology, or possibly, a general vulnerability to malignant disease for these patients. A detailed analysis of causes of death in a population-based cohort of small intestinal malignancies has not been presented before in the literature.     

The risk of developing second cancers among survivors of childhood soft tissue sarcoma

BACKGROUND: Previous studies have shown that children who are treated for soft tissue sarcoma (STS) are at increased risk for developing second cancers. However, the risk for specific cancer sites and variations in risk by treatment and STS histology remain unclear. METHODS: The study evaluated 1499 children (age < 18 years) who survived for > or = 1 year after they were diagnosed with STS and who were reported to the Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries from 1973 to 2000. RESULTS: Twenty-seven children developed 28 subsequent primary malignancies, compared with 4.5 expected malignancies based on general population rates (observed-to-expected [O/E] ratio = 6.3 (95% confidence interval [95% CI], 4.2-9.1). The risk of developing a subsequent malignancy was increased among children with rhabdomyosarcoma (observed = 11 malignancies; O/E ratio = 7.7), fibromatous neoplasms (observed = 9 malignancies; O/E ratio = 5.8), and other specified STS (observed = 7 malignancies; O/E ratio = 6.5). Initial therapy with radiation and chemotherapeutic agents was associated with a significantly higher risk of second malignancies compared with surgery alone (O/E ratio = 15.2 vs. 1.4; P < 0.0001). Elevated risks were observed for acute myeloid leukemia, cutaneous melanoma, female breast cancer, and sarcomas of the bone and soft tissue, with generally higher risks among patients who initially received combined modality therapy. Excess cancers of the oral cavity were prominent among long-term survivors. For several children, the pattern of multiple malignancies was consistent with a genetic syndrome, particularly neurofibromatosis type 1 and Li-Fraumeni syndrome. CONCLUSIONS: The risk of second malignancies was increased for all histologic types of childhood STS and was particularly high among patients who received combined modality therapy.     

Mortality after cure of soft-tissue sarcoma treated with conservation surgery and radiotherapy

BACKGROUND: The objective of the current study was to analyze the potential treatment-related mortality in long-term survivors of soft-tissue sarcoma (STS) treated with radiotherapy (RT) and conservation surgery. METHODS: Between 1960 and 2000, 629 of 1089 patients treated with conservation surgery and RT for nonmetastatic STS at the University of Texas M. D. Anderson Cancer Center never developed disease recurrence. Long-term survival and causes of death were evaluated using the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for death from all causes, cancer, and cardiac disease using standard U.S. data. RESULTS: The median follow-up was 13.2 years. The 10-year, 20-year, and 30-year actuarial survival rates were 88%, 69%, and 52%, respectively. The overall all-case mortality was 1.14 (95% confidence interval [95% CI], 0.98-1.33). The all-cause mortality exceeded that expected for female patients with an SMR of 1.48 (95% CI, 1.15-1.88), patients aged 相似文献   

Merkel cell carcinoma and multiple primary cancers.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for which causative factors remain largely unknown. The site-specific risks of multiple primary cancers associated with MCC, which may provide insight into etiologic influences, have not been quantified in large population-based studies. We estimated the long-term risk of subsequent primary tumors after a first primary MCC (1,306 patients) and the risk of second primary MCC following other first primary cancers (2,048,739 patients) within 11 population-based cancer registries which report to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1986-2002). Patients with first primary MCC were at significantly increased risk of developing a subsequent cancer [standardized incidence ratio (SIR), 1.22; 95% confidence intervals (95% CI), 1.01-1.45; observed (O = 122)], with significant excesses restricted to the first year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly elevated site-specific risks were observed for cancers of salivary gland (SIR, 11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95% CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were seen for chronic lymphocytic leukemia, and cancers of the small intestine and brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of MCC as a second primary malignancy was observed among patients with all other first primary cancers taken together. In particular, significant 3- to 7-fold excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4), chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR, 3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play a role, increased reciprocal risks suggest that MCC may share etiologic influences with other malignancies. Heightened awareness of the associations of lymphohematopoietic malignancies with MCC may facilitate early clinical recognition.     

Multiple primary soft tissue sarcomas

BACKGROUND: The synchronous or metachronous development of multiple primary soft tissue sarcomas (STS) of different histopathology has been reported only in isolated case reports. METHODS: The records of patients who developed multiple primary STS and who were treated at a tertiary cancer center between 1982 and 2003 were reviewed. RESULTS: Nine patients with multiple primary STS were identified, representing 0.2% of all patients who were treated for STS. The median age of patients at the time of initial presentation with sarcoma was 60 years (range, 51-81 years). Most patients in this series (n = 7) had metachronous development of a second primary STS. The incidence of second primary sarcomas in patients who were diagnosed previously with STS (4.0 per 10,000 population per year) was significantly greater than the incidence of primary STS in the general population (3.2 per 100,000 population per year; P < 0.01). CONCLUSIONS: Although it is an uncommon occurrence, patients who have a history of STS are at an increased risk for the development of a second primary STS.     

Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers

We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated families from Southern Sweden using data from parish and local tax authorities, as well as the Swedish Cancer Registry, Cause of Death Registry and Census Registry. 150 malignant tumours were analysed from 1145 relatives in the BRCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, the incidence for all malignant tumours was significantly increased for both BRCA1- standardised morbidity rate, SMR, 1.98, 95% confidence interval (CI) 1.59-2.45; P < 0.0001 and BRCA2- (SMR 1.79, 95% CI 1.35-2.31; P < 0.0001) associated family members. For women in BRCA1-associated families, the incidence of breast cancer (SMR 3.76, 95% CI 2.29-5.80, P < 0.0001), ovarian cancer (SMR 15.49, 95% CI 9.46-23.92, P < 0.0001), stomach cancer (SMR 5.86, 95% CI 1.60-15.01, P = 0.005) were significantly increased. Amongst men only invasive squamous cell cancer of the skin was significantly increased (SMR 6.02, 95% CI 1.96-14.05, P = 0.002). In BRCA2 associated families, female breast cancer (SMR 3.03, 95% CI 1.61-5.18, P = 0.0005) was increased after exclusion of index cases. If these were included, ovarian cancer (SMR 5.16, 95% CI 1.89-11.24, P = 0.001), invasive cervical cancer (SMR 4.21, 95% CI 1.15-10.79, P = 0.016), male breast cancer (SMR 290.52, 95% CI 125.42-572.43, P < 0.0001), and prostate cancer (SMR 2.21, 95% CI 0.89-4.56, P = 0.042) were significantly increased. The increased risk for ovarian cancer in BRCA2 related families were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer types do not appear to be greatly increased in BRCA1- and BRCA2-associated families and does not warrant specific clinical follow-up in carriers.     

Increased mortality rates in young and middle-aged patients with malignant germ cell tumours

Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged 相似文献   

Risk of mortality and cancer incidence in Barrett's esophagus.

BACKGROUND: There are very few prospective follow-up studies of Barrett esophagus (BE) cohorts assessing the risk of extraesophageal cancer incidence or mortality. Such studies are necessary in order to understand the overall risks of cancer and death experienced by patients with BE. METHODS: A cohort of 502 patients with BE were identified at Leeds General Infirmary, England. Mortality and cancer incidence information were provided by the Office for National Statistics. Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) were calculated using indirect standardization. RESULTS: All-cause mortality was found to be elevated in patients with BE [SMR, 1.21; 95% confidence interval (95% CI), 1.06, 1.37] and remained so after esophageal cancers were excluded (SMR, 1.16; 95% CI, 1.01-1.32). Increased mortality risks were also found for malignant neoplasms of the esophagus (SMR, 7.26; 95% CI, 3.87-12.42) and diseases of the digestive system (SMR, 2.03; 95% CI, 1.11-3.40). The remaining disease categories produced no altered risk estimates. Circulatory disease mortality was borderline statistically significant (SMR, 1.24; 95% CI, 1.00-1.52; P = 0.053) for those with a specialized intestinal metaplasia diagnosis of BE. In the cancer incidence analyses, esophageal malignancies (SIR, 8.66; 95% CI, 4.73-14.53) and esophageal adenocarcinomas (SIR, 14.29; 95% CI, 7.13-22.56) were found to be increased in BE. All remaining analyses provided unaltered risks, including that of colorectal cancer. CONCLUSIONS: This study has shown evidence of an increased risk of esophageal cancer incidence and mortality in BE. It has also shown that those who have a histologic BE diagnosis may also have an increased risk of circulatory disease mortality.     

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.     

Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study

PURPOSE: To assess long-term cause-specific mortality in breast cancer patients. PATIENTS AND METHODS: We studied mortality in 7425 patients treated for early breast cancer between 1970 and 1986. Follow-up was 94% complete until January 2000. Treatment-specific mortality was evaluated by calculating standardized mortality ratios (SMRs) based on comparison with general population rates and by using Cox proportional hazards regression. RESULTS: After a median follow-up of 13.8 years, 4160 deaths were observed, of which 76% were due to breast cancer. Second malignancies showed a slightly increased SMR of 1.2 (95% confidence interval [CI], 1.0-1.3). Radiotherapy (RT) as compared with surgery was associated with a 1.7-fold (95% CI, 1.2-2.5) increased mortality from cardiovascular disease (CVD). After postlumpectomy RT, no increased mortality from CVD was observed (hazard ratio, 1.0; 95% CI, 0.5-1.9). Postmastectomy RT administered before 1979 and between 1979 and 1986 was associated with a 2-fold (95% CI, 1.2-3.4) and 1.5-fold (95% CI, 0.9-2.7) increase, respectively. Patients treated before age 45 experienced a higher SMR (2.0) for both solid tumors (95% CI, 1.6-2.7) and CVD (95% CI, 1.3-3.1). CONCLUSION: Currently, a large population of breast cancer survivors is at increased risk of death from CVDs and second cancers, especially when treated with RT at a young age. Patients irradiated after 1979 experience low (postmastectomy RT) or no (postlumpectomy RT) excess mortality from CVD.     

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.     

Cancer risk in women with previous breast cancer.

BACKGROUND: Excess risks of several second neoplasms following breast cancer have been reported. However, these risks have still to be quantified. PATIENTS AND METHODS: We considered 9,729 breast cancer patients registered by the Swiss Cancer Registries of Vaud and Neuchatel (covering about 786,000 inhabitants) and followed up from 1974 to 1998. RESULTS: Overall, 443 second primary neoplasms (other than second primary breast cancers) were observed versus 389 expected [standardised incidence ratio (SIR): 1.14; 95% confidence interval (CI) 1.04-1.25]. The SIRs were above unity for endometrium (SIR = 1.5), ovary (1.3), colorectum (1.1), gallbladder (1.4), cutaneous malignant melanoma (1.4), kidney (1.4), lymphomas (1.4) and leukaemias (1.2), as well as for selected tobacco-related neoplasms. The largest excess risk was found for soft tissue sarcomas (STS) with 10 cases observed versus 3.1 expected (SIR = 3.2; 95% CI 1.5-5.9). Of these, eight occurred in potentially irradiated areas. CONCLUSIONS: This analysis confirms the existence of a modest excess in several neoplasms occurring after breast cancer. The substantial excess of STS confirms the strong association between irradiation and STS.     

Suicides among cancer patients in Estonia: a population-based study

The objective of this study was to determine the suicide risk among cancer patients in Estonia. This risk was examined in a cohort of 65,419 persons diagnosed with cancer in 1983-1998. Standardised mortality ratios (SMR) were calculated using the suicide rates of the population of Estonia as a reference. During 192,078 person-years of follow-up between 1983 and 2000, 197 suicides occurred in the cohort. An increased suicide risk was found for men (SMR=1.73; 95% Confidence Interval (CI) 1.45-2.01), but not for women (SMR=0.50; 95% CI 0.37-0.66). Men had the highest risk 90-179 days following their diagnosis (SMR=4.27; 95% CI 2.81-6.21). During this time interval, among men, the risk was more pronounced for cancers of the oesophagus (SMR=35.63; 95% CI 9.71-91.22) and pancreas (SMR=14.53; 95% CI 1.76-52.50). This study provides further evidence that cancer is a risk factor for suicide, at least in men.     

Second cancers in patients with brain tumours--impact of treatment

The records of the Finnish Cancer Registry from 1953 to 1994 were used to assess the risk of subsequent primary cancer among 14,493 brain tumour patients. They had been treated with surgery only (n = 9804), radiotherapy (n = 4099), chemotherapy and radiotherapy (n = 493) or chemotherapy alone (n = 97). By the end of 1994, 403 subsequent primary cancers were registered in these patients, whilst the expected number based on national incidence was 332. The standardised incidence ratio (SIR) was 1.2 (95% confidence interval (CI) 1.1-1.3). A significant excess risk of tumours in the central nervous system (CNS) including meningeomas (SIR 2.6, 95% CI 1.7-3.8), non-Hodgkin's lymphoma (SIR 2.6, 95% CI 1.6-4.1) and skin melanoma (SIR 1.9, 95% CI 1.0-3.1) was observed. CNS tumours were observed in excess among patients treated with surgery alone (SIR 2.0, 95% CI 1.2-3.2) and with radiotherapy (SIR 5.1, 95% CI 2.5-9.4). In conclusion, brain tumours are associated with an increased risk of both CNS second tumours and non-CNS second cancers, especially non-Hodgkin's lymphoma and melanoma. A moderately increased risk of second tumours in the CNS was observed among brain tumour patients treated with surgery only and a larger excess among those treated with radiotherapy.     

Mortality from cancer and other causes in parents of children with cancer: a population-based study in Piedmont, Italy.

This population-based study (the largest on this issue conducted in Southern Europe) has examined mortality among the parents of 2622 children diagnosed with cancer in Piedmont during 1967-1994. Parents were followed up from the date of the index child's birth until the end of 2000, yielding a total of 118 090.7 person-years of observation. Standardized mortality ratios (SMRs) were estimated using mortality rates for the whole population of Piedmont as the reference. Among mothers, total mortality was similar to that expected [SMR 1.02, 95% confidence interval (CI) 0.85-1.23, 117 cases]. A reduced risk of mortality was seen in fathers (SMR 0.91, 95% CI 0.81-1.02, 293 cases); this was largely due to causes other than cancer and the reduction in risk disappeared after the index child's death (SMR 0.98, 95% CI 0.84-1.15, 168 cases). Deaths from cancers of the lymphohaematopoietic system were in excess among mothers (SMR=2.13, 95% CI 1.02-3.92, 10 cases) and breast cancer deaths were in excess specifically among mothers of leukaemic children (SMR 2.32, 95% CI 1.16-4.14, 11 cases). Three mothers dying with breast cancer had index children who had been diagnosed with a bone sarcoma. Parental cancer of the respiratory tract was significantly associated with both tumours of the central nervous system and Hodgkin's lymphoma in the index child. The excess risks identified here may be due to genetic factors or due to parental psychological stress consequent to cancer in a child that may lead to increased mortality either through the direct effects of stress or through consequent changes in lifestyle.     

Risk of malignancy among patients with rheumatic conditions

Previous studies have described an increased risk of malignancy in subjects diagnosed with rheumatic conditions, most notably rheumatoid arthritis (RA). Our aim was to quantify and compare risks for site-specific malignancy among hospitalized patients with RA, osteoarthritis (OA) and other rheumatic conditions in a nationwide, population-based cohort. Subjects were identified from Scottish hospital in-patient records from 1981 to 1996 and followed up by computer linkage of the Scottish Cancer Registry and the national registry of deaths. Expected cancer incidence was calculated from national cancer rates and related to the observed incidence by the standardized incidence ratio (SIR). Among RA patients, there was an increased risk for hematopoietic [males SIR= 2.13, 95% confidence interval (CI) 1.7-2.7; females SIR = 1.76, 95% CI 1.5-2.1], lung (males SIR = 1.32, 95% CI 1.2-1.5; females SIR = 1.44, 95% CI 1.3-1.6) and prostate (SIR = 1.26, 95% CI 1.0-1.6) cancers. Reduced risk were seen for colorectal cancer (males SIR = 0.87, 95% CI 0.7-1.1; females SIR = 0.71, 95% CI 0.6-0.9) and, among females, stomach cancer (SIR = 0.70, 95% CI 0.5-1.0). The excess risk for hematopoietic cancer and the reduced risk for colorectal and stomach cancers were sustained over 10 years of follow-up. An overall decreased risk of cancer was observed for patients with OA; the greatest reductions were observed for colorectal (males SIR = 0.88, 95% CI 0.8-1.0; females SIR = 0.84, 95% CI 0.8-0.9), stomach (males SIR = 0.79, 95% CI 0.7-0.9; females SIR = 0.66, 95% CI 0.6-0.8) and lung (males SIR = 0.72, 95% CI 0.7-0.8; females SIR = 0.84, 95% CI 0.8-0.9) malignancies, with decreased risks generally still evident at 10 years of follow-up. Our results support several previous findings regarding the incidence of hematopoietic and colorectal malignancies in RA patients. In addition, we have shown a large decrease in stomach cancer among patients with OA and females with RA that warrants further investigation since it may provide clues to possible prevention strategies. To further our knowledge about the underlying mechanisms of altered risk in cancer patients with rheumatic conditions, population studies requiring primary data collection are required.     

Multiple primary malignancies in association with soft tissue sarcomas

BACKGROUND: Modern cancer treatment has increased the survival of patients with various malignancies substantially. One of the late sequelae of successful treatment is the development of a second malignant tumor. However, in many cases of second primary tumors, exposure to chemotherapy or radiation therapy is not evident, and it should be postulated that the putative mechanism for the development of the second tumor is different. In the current series, the association between soft tissue sarcoma (STS) in adults and the development of other primary malignancies was studied. METHODS: A retrospective search of the data files of 610 patients with STS or bone sarcomas who were treated at the study institution between January 1995 and December 1999 was performed. All files regarding patients with STS who developed a second malignant tumor were retrieved for analysis. RESULTS: Of 375 patients with STS, 28 (7.5%) developed other malignant neoplasms either before or after the diagnosis of STS. STS as the first tumor occurred in 14 patients (ages 16-72 years). Only three patients were treated with chemotherapy for their sarcoma. Radiation therapy was administered to five patients as an adjuvant to surgery for the first tumor. The second tumor types mainly included STS and renal cell carcinoma. The time interval between the diagnosis of the STS and the second malignancy was 0 (for synchronous tumors) to 21 years. Three patients developed a third primary tumor within 3 years after the diagnosis of the second tumor. The median overall survival was > 78 months. Fourteen patients (ages 35-87 years) had a first primary tumor other than STS (mainly breast carcinoma and genitourinary malignancies). The second tumors (mainly STS) appeared within 0 (for synchronous tumors) to 27 years. The median overall survival for the 14 patients in this group from the time of diagnosis of the first tumor was > 102 months. CONCLUSIONS: The phenomenon of two or three primary neoplasms developing in patients in whom one of the tumors was STS occurs at a rate of 7.5%, a significantly higher rate than that reported for the occurrence of STS among the general cancer population (1%). The majority of cases occur incidentally. The clinical implication includes the need to search for an occult second primary tumor in patients with STS as an integral part of their follow-up. This is especially true in patients with primary malignant fibrous histiocytoma who demonstrate a risk for developing a renal cell carcinoma.     

Second malignancies following pure seminoma

PURPOSE: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. PATIENTS, METHODS: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the study because they already had had either a contralateral testicular germ cell tumor or another malignancy. 758 patients received radiotherapy, 76 underwent chemotherapy, 5 had surveillance only. The expected rate of second cancers was calculated according to the data of the cancer registry of Saarland, Germany. RESULTS: Twenty-two second cancers (13 contralateral testicular tumors, 9 extratesticular malignancies) were recorded. The overall risk of having a second cancer was RR = 4.8 (95% CI 3. 0-7.3). The risk of having a subsequent testicular tumor is RR = 44. 8 (95% Cl 23.9-76.7). 1.1% of the patients developed a nontesticular second tumor. The risk of having a nontesticular second cancer is RR = 2.1 (95% CI 1.0-4.0). A significantly increased risk was observed for renal cell cancer as well (RR = 12.5; 95% Cl: 1.5-45.1). Increased RR without reaching statistical significance were found for rectal cancer (RR = 5.0; 95% Cl: 0.1-27.9) and non-Hodgkin lymphoma (RR = 6.7; 95% CI 0.2-37.1). None of the second cancers were directly located within the radiation field; 5 neoplasms arose at the border of the radiation field. CONCLUSIONS: This study confirmed the increased risk of having a second testicular germ cell cancer. There is also a small but definitely increased overall risk of having a nontesticular second cancer. Treatment-unrelated factors - possibly genetic predisposition - must be considered for a substantial number of these second tumors, since in the present study the follow-up was rather short and most of the second cancers were located outside of the radiation fields. In particular, the association of renal cancer with testicular cancer appears to be a more than chance occurrence. Second cancer is a real hazard following treatment of testicular cancers and should always be considered during follow-up.     

Increased risk of colon cancer after external radiation therapy for prostate cancer

Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population-based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person-years. At the end of follow-up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7-6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8-7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2-7.2). The risk of colon cancer was increased in the period of 5-9 years after diagnosis (SIR = 4.7, 95% CI: 2.0-9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.