Subsequent Malignant Neoplasms Research Articles

Subsequent malignant neoplasms in survivors of childhood cancer: Childhood Cancer Survivor Study (CCSS) studies

Survival of children diagnosed with cancer has improved markedly, because of improvements in chemotherapy and radiation treatment protocols, better diagnosis, and risk classification and improved supportive care. Significant numbers of survivors are now entering their 30s and 40s, and data indicate that excess mortality continues in this group at least as long as 25 to 30 years after treatment. The Childhood Cancer Survivor Study (CCSS) is a large cohort study of 14,054 childhood cancer survivors who have been followed for over 13 years, with a median time from diagnosis now approaching 20 years. This cohort offers an extraordinary opportunity to study therapy-associated subsequent malignant neoplasms, and has allowed improved definition of incidence and risk factors for subsequent breast and thyroid cancer. The collection of genetic samples from members of the cohort has allowed the inclusion of studies of genetic susceptibility to subsequent malignant neoplasms in this population with a uniquely well-defined carcinogenic exposure. The planned formation of a new CCSS cohort, treated with more modern therapy, will allow the extension of these studies to younger populations and will define their experience of subsequent malignant neoplasms.

Twenty Years of Follow-Up among Survivors of Childhood and Young Adult Acute Myeloid Leukemia (AML): A Report from the Childhood Cancer Survivor Study (CCSS).

Survival rates for childhood AML continue to improve. Limited data exist on the comprehensive assessment of late medical and social effects experienced by these aggressively treated individuals. This analysis includes 272 5-yr survivors of AML participating in the CCSS diagnosed ≤ age 21, between 1970–1986. AML survivors who received a blood or marrow transplant are excluded from the current analysis. Comparisons among treatment groups and to a sibling control group are age and gender adjusted. Survivors (55% female) were on average 7 yrs old at dx and 28 yrs at follow-up, 56% received chemotherapy only, 34% chemotherapy/RT. Average follow-up was 22.6 yrs (16.1–33.5). Among these 5-yr survivors, overall survival was 97% (95% CI, 94–98%) at 10 yrs and 94% (95% CI, 92–97%) at 20 yrs. Six individuals reported 8 recurrences a mean of 11.1 yrs (5.6–16.6) from diagnosis, 2 died from relapse, 1 from congestive heart failure (CHF), and 1 from a myocardial infarction (MI). All cause standardized mortality ratio was 4.7 (95% CI 2.8–7.5). Cumulative incidence of recurrent AML at 10 and 20 years was 1.8% (95% CI 0.2–3.4%) and 3.7% (95% CI 1.4–5.9%), respectively. Eight survivors reported 10 subsequent malignant neoplasms (SMN) (5 breast cancers, 3 CNS tumors, 1 ovarian tumor, 1 salivary gland tumor) a mean of 18.7 yrs (9.2–26.4) from diagnosis, 3 with a history of RT exposure. SMN cumulative incidence at 20 yrs was 1.6% (95% CI 0.02–3.3%) with a standardized incidence ratio of 3.2 (95% CI 1.4–6.0). Six cardiac events (5 CHF and 1 MI) occurred a mean of 16.4 yrs (12.8–18.4) from diagnosis, 20-yr cumulative incidence 2.4% (95% CI 0.5–4.4%). Among those aged 25 yrs or more, marriage rates were similar among AML survivors and the general U.S. population (59%), but lower compared to siblings (69%) (p<0.01). College graduation rates were lower among survivors compared to siblings, but higher than in the general population (42% vs. 52% vs. 34%, respectively, p<0.01). No significant difference in graduation rates was found among those treated with or without CNS directed RT (p=0.9). All survivors and siblings were employed (100%) and most had health insurance (93% vs. 90%). Long-term survival from childhood AML greater than 5 yrs from diagnosis is favorable. Late occurring medical events remain concerning. Marriage and education rates may be lower than expected within individual family units; yet not significantly different from the U.S. population.

204: Secondary Bone and Soft Tissue Sarcomas In Children Treated for Hodgkin Lymphoma

204: Secondary Bone and Soft Tissue Sarcomas In Children Treated for Hodgkin Lymphoma

Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer. Subsequent malignant neoplasm history was determined in 13,136 participants (surviving > or = 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data. In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9). Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.

Sarcomas as a subsequent malignancy in survivors of pediatric malignancy:The Childhood Cancer Survivor Study

8515 Background: Subsequent sarcomas (SS) in childhood cancer survivors have not been well-studied, with prior studies limited to smaller series of bone tumors. Methods: The Childhood Cancer Survivor Study (CCSS) is a multi-institutional cohort of 14,352 five-year survivors of childhood cancers, including leukemia, lymphoma, central nervous system tumors, neuroblastoma, kidney tumors, bone tumors and soft tissue sarcomas (STS), diagnosed between 1970 and 1986. SS were ascertained through self-administered questionnaires and confirmed with pathology reports. The risk factors for developing second sarcomas were assessed through univariate analysis as well as multivariate Cox regression analysis. Results: We describe a series of 91 SS [osteosarcoma (n=27), Ewing’s/PNET (n=5), rhabdomyosarcoma (n=3), other STS (n=36), malignant peripheral nerve sheath tumor (n=13), other (n=7)] The incidence rate of SS was 3.2 cases per 1,000 person-years (py) from 28,301 py of observation after primary cancer diagnosis. Risk of SS was associated with primary diagnosis (p<0.001), history of other subsequent malignant neoplasm (p=0.009), anthracycline exposure (p=0.009), alkylator exposure (p=0.002) and radiation therapy (RT; p<0.001) in univariate analysis. In a multivariate model, risk factors for the development of SS included anthracycline exposure and previous RT with respective rate ratios (RR) of 2.54 (p=0.008) and 2.58 (p=0.005), with these risks further influenced by primary diagnosis (p<0.001). Subgroup analysis of Hodgkin’s disease survivors revealed that alkylating agent exposure was associated with the development of SS with a RR of 4.26 (p=0.06). Subgroup analysis of STS survivors revealed that younger age at primary cancer diagnosis was associated with an increased risk of developing SS (p=0.01). Conclusions: Survivors of childhood malignancy are at increased risk of developing SS. Identified risk factors include exposure to anthracyclines, alkylators and RT, within diagnosis-specific subgroups. Analyses are underway to investigate standardized incidence ratios and absolute excess risk of SS in survivors, dose-response relationships as well as family history of cancer. No significant financial relationships to disclose.

Risk of rare adult-type carcinomas as a subsequent malignant neoplasm in survivors of childhood cancer: The Childhood Cancer Survivor Study

8530 Background: Subsequent malignant neoplasms (SMNs) are a leading cause of late mortality in survivors of childhood cancer. Using the Childhood Cancer Survivor Study (CCSS) cohort, we determined the risk of carcinomas occurring as SMNs excepting breast, thyroid and skin cancers. Methods: A retrospective cohort of 14,352 five-year survivors of childhood cancers treated at 25 US and Canadian institutions was assembled. SMNs were ascertained through self-administered questionnaires and confirmed with pathology reports. Cumulative incidence, age- and gender-matched standardized incidence ratios (SIRs) were calculated. Results: In 71 individuals, 71 carcinomas of interest were found at a median age of 27 years (range 10–44 years) and a median elapsed time of 15 years (range 6–28 years) from first malignancy. Twenty-five (35%) SMNs occurred in the genitourinary system, 23 (32%) in the head and neck area, 16 (23%) in the digestive tract, 4 (6%) in the thorax and the remainder (4%) in other sites. Fifty-nine subjects (83%) had received radiation therapy, 49 (69%) had a history of alkylator therapy, and 8 (11%) had a history of epipodophyllotoxin therapy. Forty-two carcinomas (59%) arose in a radiation field. An excess of carcinomas was found following all childhood diagnoses, and was highest for neuroblastoma (SIR = 24.2 [95% confidence interval [CI] = 12.6–46.5]), soft tissue sarcomas (SIR = 6.2, [95% CI = 3.5–11]) and Wilms tumor (SIR = 4.8 [95% CI = 1.5–14.8]). There was a significant excess of carcinomas in most of the morphology types examined and was greatest for mucoepidermoid neoplasms (SIR=34.0 [95%CI= 19.3–59.9]) and renal cell carcinomas (SIR = 13.3 [95%CI = 6.7–26.7]). The 20-year cumulative incidence for all SMNs in this report is 0.45%. Conclusions: Childhood cancer survivors are at increased risk of developing subsequent adult-type carcinomas, but the cumulative incidence is low. Further analyses of the contribution of patient and treatment factors to the increased risk of carcinomas in this population are in progress. No significant financial relationships to disclose.

Risk of rare adult-type carcinomas as a subsequent malignant neoplasm in survivors of childhood cancer: The Childhood Cancer Survivor Study

8530 Background: Subsequent malignant neoplasms (SMNs) are a leading cause of late mortality in survivors of childhood cancer. Using the Childhood Cancer Survivor Study (CCSS) cohort, we determined the risk of carcinomas occurring as SMNs excepting breast, thyroid and skin cancers. Methods: A retrospective cohort of 14,352 five-year survivors of childhood cancers treated at 25 US and Canadian institutions was assembled. SMNs were ascertained through self-administered questionnaires and confirmed with pathology reports. Cumulative incidence, age- and gender-matched standardized incidence ratios (SIRs) were calculated. Results: In 71 individuals, 71 carcinomas of interest were found at a median age of 27 years (range 10–44 years) and a median elapsed time of 15 years (range 6–28 years) from first malignancy. Twenty-five (35%) SMNs occurred in the genitourinary system, 23 (32%) in the head and neck area, 16 (23%) in the digestive tract, 4 (6%) in the thorax and the remainder (4%) in other sites. Fifty-nine s...

Second malignant neoplasms following hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation is being successfully used to treat a variety of malignant and nonmalignant disorders. This therapy has resulted in an increasing number of survivors who are at risk for adverse long-term outcomes, including the development of second and subsequent malignant neoplasms. We review the incidence and spectrum of posttransplantation malignancies and discuss risk factors and future directions for research.

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Overview of the effects of cancer therapies: the nature, scale and breadth of the problem

Over the past 30 years, the striking improvements in the survival rates of patients with childhood cancers are due, in large part, to the use of aggressive treatment strategies. These therapeutic modalities are associated with a variety of late complications that span a spectrum from minor and treatable to serious and occasionally lethal. Nearly one-quarter of the late deaths in survivors of childhood cancer can be attributed to a treatment-related effect, for example, a subsequent malignant neoplasm or cardiac dysfunction. The risk of late death due to causes other than recurrence is greatest in survivors treated with the combination of chemotherapy and radiotherapy. Among the 650 survivors followed in the Long-Term Follow-Up Clinic at the Memorial Sloan-Kettering Cancer Center, the most common sequelae are endocrine complications, which are seen in 40% of the patients. Growth hormone deficiency, primary hypothyroidism and primary ovarian failure are the endocrine disorders observed most often.

Bowen disease and risk of subsequent malignant neoplasms: a population-based cohort study of 1147 patients.

To address the long-standing question of whether patients with Bowen disease are at increased risk of internal malignant neoplasms. A total of 1147 Danish patients diagnosed between 1978 and 1993 as having Bowen disease at nongenital sites were followed up for 6463 person-years for cancer occurrence up to 16 years after the skin lesion. Standardized incidence ratios (SIRs)--the ratios of observed-to-expected numbers of cancer--served as measures of relative risk. The observed number of noncutaneous cancers occurring in the cohort (n = 115) was close to expected (n = 103.0) (SIR = 1.1; 95% confidence interval, [CI], 0.9-1.3). However, nonmelanoma skin cancer (SIR = 4.3; 95% CI, 3.5-5.4; n = 83), lip cancer (SIR = 8.2; 95% CI, 2.6-19.1; n = 5), and, among men, leukemia (SIR = 3.2; 95% CI, 1.04-7.5; n = 5) occurred in excess. Patients with Bowen disease do not appear to constitutionally be at any unusually high general cancer risk. The increased risk of invasive skin and lip cancers is likely due to the common risk factor of UV light.

Literature Review: Hematology/Oncology: Risk of Subsequent Malignant Neoplasms among 1,641 Hodgkin's Disease Patients Diagnosed in Childhood and Adolescence: A Population-Based Cohort Study in the Five Nordic Countries

Literature Review: Hematology/Oncology: Risk of Subsequent Malignant Neoplasms among 1,641 Hodgkin's Disease Patients Diagnosed in Childhood and Adolescence: A Population-Based Cohort Study in the Five Nordic Countries

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.

Survival of stage I lung cancer patients with previous or subsequent primary malignant neoplasms

Survival of stage I lung cancer patients with previous or subsequent primary malignant neoplasms

Risk of subsequent malignant neoplasms among 470,000 cancer patients in Finland, 1953-1991.

Because of increasing numbers of incident cancers and improving survival rates, more and more cancer patients are at risk of subsequent primary malignant neoplasms. The potential carcinogenicity of cancer therapies raises further concern regarding this unwanted long-term side effect. The objective of this cancer-registry-based study was to assess the trends in the risk of subsequent primary malignancies among cancer patients on a nationwide public-health level. The 470,000 cancer patients registered between 1953 and 1991 in Finland were followed up for subsequent primary neoplasms, and 19,800 subsequent malignant neoplasms were observed, yielding an overall standardized incidence ratio (SIR) of 1.00 for men and 1.25 for women. Substantial variation was observed in the SIR by the site of subsequent malignancy. The adjusted relative risk derived from multiple regression analyses showed only a slight increase by follow-up interval. Overall, the excess relative risk of subsequent malignancies was low, since the majority of cancer patients are old and at low relative risk. Patients under the age of 50 years, however, were at 70% increased risk, and the overall relative risk increased by 50% from the 1950s to the 1980s. Subsequent neoplasms among cancer patients do not pose a major public-health problem, but the possibility of subsequent cancers must be borne in mind in decisions concerning therapy and in clinical follow-up.

Risk of subsequent malignant neoplasms in patients with deep-vein thrombosis

Risk of subsequent malignant neoplasms in patients with deep-vein thrombosis

Risk of subsequent malignant neoplasms in patients with deep-vein thrombosis

Risk of subsequent malignant neoplasms in patients with deep-vein thrombosis

Long-term risk of second malignant neoplasm after a cancer in childhood.

The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.

Deep venous thrombosis and pulmonary embolism: risk of subsequent malignant neoplasms: Griffin MR, Stanson AW, Brown ML, et al. Arch Intern Med 1987;147:1907–1911

Deep venous thrombosis and pulmonary embolism: risk of subsequent malignant neoplasms: Griffin MR, Stanson AW, Brown ML, et al. Arch Intern Med 1987;147:1907–1911

Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms

• We conducted a noncurrent prospective study of all Olmsted County, Minnesota, residents who had had a lowerextremity venogram, pulmonary angiogram, or lung scan performed because of suspicion of deep venous thrombosis or pulmonary emboli. One hundred thirteen cancer-free patients were followed for 386 person-years from the date of procedure. Nine subsequent cancers were observed compared with 4.5 expected (relative risk, 2.0; 95% confidence interval, 0.9 to 3.8), using total cancer incidence rates for the Rochester, Minn, population. Five hundred seventeen cancer-free controls were followed for 2072 person-years. Twenty subsequent cancers were observed compared with 11.6 expected, yielding a relative risk of 1.7 (95% confidence interval, 1.1 to 2.7). When cases and controls were compared directly, no statistically significant difference in cancer-free survival was found. (<i>Arch Intern Med</i>1987;147:1907-1911)