Characterization of Second Primary Malignancies in Mucosa-Associated Lymphoid Tissue Lymphomas: A SEER Database Interrogation.

Introduction: Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016.Methods: Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas.Results: During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma.Conclusion: These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.     

High incidence of other neoplasms in patients with low-grade gastric MALT lymphoma

BACKGROUND: Low-grade gastric MALT lymphoma is an uncommon tumour for whicha close association with chronic Helicobacter pylori infectionhas been suggested. However, given the rarity of MALT lymphomaof the stomach despite the high prevalence of H. pylori infection,it seems plausible that genetic host factors might play a fundamentalrole in gastric lymphomagenesis. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 83 patientswith low-grade gastric MALT, all of whom resided in a geographicarea (southern Switzerland and northern Italy) where the incidenceof gastric tumours appears to be uncommonly high. RESULTS: One or more additional cancers were observed in17 of 83 patients(20%, 95% CI 12% to 31%) for a total of 23 tumours. Of these,5 were diagnosed prior to, 12 con-comitantly with, and 7 afterthe gastric MALT lymphoma. Eleven patients had a single additionalsolid tumour (13%, 95% CI 7% to 22%); 3 patients had non-Hodgkin'slymphoma and one had Hodgkin's disease. Multiple additionalcancers were present in 3 cases. Nine of 83 patients have diedand 8 of them of a second cancer. CONCLUSIONS: Unexpectedly an extraordinarily large number of patients withother malignancies was observed in this series. The reasonsfor this finding are still unknown, but genetic alterationsare speculated to play an important role. stomach, MALT lymphoma, non-Hodgkin's lymphoma, solid tumours, second neoplasms     

Other cancers in patients with gastric MALT lymphoma

Patients with Hodgkin's disease and nodal non-Hodgkin's lymphomas seem to have an excess risk for other cancers. A high incidence of other cancers has also been found in some series of patients with gastric MALT lymphomas. In a series of 136 patients with gastric MALT lymphomas the occurrence and features of other cancers have been described. In order to evaluate their occurrence statistically (excluding skin cancers) standard incidence ratios (SRI) have been calculated, using the incidence rates of a Cancer Registry in Spain as a reference. A Cox's multivariate proportional hazard model was fitted in order to evaluate the influence of age, sex, histological grade and treatment with chemotherapy or chemotherapy plus radiotherapy in the development of other non-skin cancers occurring after the diagnosis of MALT lymphoma. Other cancers were detected in 16 of the 136 patients (11.7%); the other cancer was detected prior to MALT gastric lymphoma in 6 patients (4.41%), concomitantly in 4 (2.9%) and after diagnosis of the lymphoma in 6 (4.41%). Other cancers occurred in 14.4% of the male and in 8.3% of the female patients; in 12% of the patients with low grade and in 11% of the patients with high grade lymphomas. Of the 6 cancers that occurred after diagnosis of the gastric lymphoma, 3 did in the 80 patients (3.7%) that had been treated with chemotherapy, 1 in the 3 cases (33%) treated with chemotherapy and radiotherapy and 2 in the 53 patients (3.7%) who had not received chemotherapy or radiotherapy. The most frequent other cancers were lymphoid neoplasms and gastric carcinoma. There was not an excess of other cancers in the whole cohort or in the sex or histological grade strata. There was an excess close to significance (SIR =2.59; 95% CI:0.98-6.88) in the patients under 50 years of age. In the Cox's analysis, age, sex, histological grade and treatment did not influence the occurrence of other cancers after the diagnosis of lymphoma. In conclusion, in patients with gastric MALT lymphoma other cancers also occur. An excess incidence was not demonstrated, although it may exist in patients under 50 years. Of special importance is the occurrence of gastric cancer that appears concomitantly or after gastric lymphoma.     

Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: The aim was to examine characteristics and treatment results of patients with mucosa-associated lymphoid tissue (MALT) non-Hodgkin's lymphomas. PATIENTS AND METHODS: Epidemiological and clinical features of 97 patients with MALT lymphoma from the Hellenic Cooperative Oncology Group registry were analysed retrospectively for their prognostic significance in progression-free survival (PFS) and overall survival (OS). Comparisons were made between patients with gastric and nongastric sites of primary lymphoma and between different therapeutic modalities. RESULTS: Sixty-five patients presented with gastric and 32 with nongastric lymphomas. The most frequent locations of nongastric lymphomas were the bowel, lung and parotid. Gastric lymphomas occurred more frequently in males and younger patients compared with nongastric lymphomas. Seventy-four per cent of patients had early (Ann Arbor stages I-II) and 26% had advanced (stages III-IV) disease. The median PFS for the entire population was 44 months. At 5 years, 47% of patients were progression free and the OS rate was 80%. The most reliable prognostic factor for PFS and OS was the Ann Arbor stage; 5-year PFS was 67% versus 13% and 5-year OS 91% versus 51% for patients with early versus advanced disease, respectively (P < 0.001). Of the patients treated with chemotherapy only, 87% achieved an objective response and 71% complete response. Surgery did not offer survival benefit compared with chemotherapy in localised gastric lymphoma. CONCLUSION: MALT lymphomas represent a distinct disease entity with widespread extranodal origin, indolent clinical course and high chemosensitivity. Ann Arbor stage was the most reliable prognostic and predictive factor.     

Incidence of second neoplasms in patients with MALT lymphoma: No increase in risk above the background population

Background: Lymphomas of mucosa associated lymphoid tissue (MALT) are a special type of extranodal lymphoma, possibly related to chronic antigenic stimulation. Increased cancer susceptibility may also contribute to the development of MALT lymphoma (MALToma). It has been suggested that patients with MALToma have an increased incidence of other malignancies.Patients and methods: We retrospectively reviewed the histology and clinical records of 147 patients with MALToma, including 51 cases of gastric MALToma. The incidence of any second malignancy was confirmed with a provincial registry. The relative rates of cancer, excluding MALToma, were calculated relative to the background population of the same age group and secular year.Results: A total of 41 tumors occurred in 32 patients (21%), including 22 solid tumors. The incidence of solid tumors in the gastric MALToma group was 15%. Seven patients had two or more second malignancies. Cancer occurred before diagnosis of MALToma in 29 cases, concurrent with MALToma in three, and after MALToma in nine. Follow-up of the surviving patients is short (median 17.6 months). The relative rate from birth of a second malignancy was 0.86 in the whole group (90% confidence interval (CI): 0.62–1.16) and 0.95 (90% CI: 0.55–1.54) in the gastric MALToma group. The rates were roughly the same if skin cancers were excluded.Conclusions: The incidence of second cancers in this series is similar to previous reports. However, when compared to an age-matched population followed for the same period of time, MALToma patients do not appear to have a statistically significant increased rate of cancers.     

Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT.

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.     

Nongastric marginal-zone B-cell MALT lymphoma: prognostic value of disease dissemination

The aim of this study is to describe the clinical features and define the prognostic significance of disease dissemination in a large series of nongastric marginal-zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. We studied 208 patients with nongastric marginal-zone B-cell MALT lymphoma diagnosed and treated from 1991 to 2004. Ninety percent of the patients had a single site of MALT involvement--skin (26%), salivary glands (18%), orbit (14%), Waldeyer's ring (13%)--and 39% and 28% had nodal involvement and bone marrow involvement, respectively. After a median follow-up of 2.7 years, the median event-free survival (EFS) time was 2.4 years, and the median overall survival (OS) time was not reached. On univariate analysis, the features significantly associated with longer EFS and OS times were the following: single MALT site involvement (OS), localized disease (EFS and OS), no nodal disease (EFS and OS), skin and orbit lymphoma (OS), and stage IV disease without bone marrow involvement (OS). On multivariate analysis, both bone marrow and nodal involvement were associated with shorter OS. This study describes the clinical features and the natural history of nongastric marginal-zone lymphomas and highlights that the dissemination to lymph nodes and bone marrow is associated with a poorer outcome.     

Cancer risk in carbon electrode workers: an overview of epidemiological evidence.

Carbon or graphite electrode manufacturing may lead to exposure to polycyclic aromatic hydrocarbons, some of which are considered human carcinogens. To provide comprehensive evidence on cancer risk, we have considered five cohort studies from the USA, France, Sweden and Italy, including about 6,500 workers and 80,000 man-years at risk. In two studies providing data on incidence, 52 incident cases of all neoplasms were reported versus 56.28 expected, corresponding to a standardized incidence ratio (SIR) of 0.92. There were nine cases of lung cancer (SIR=0.91) and three of urinary cancers (SIR=0.81). Four studies gave data on mortality. Overall, 853 deaths were observed versus 1,065.2 expected, corresponding to a standardized mortality ratio (SMR) of 0.80 (95% confidence interval, CI, 0.75-0.86). There were 269 deaths from all neoplasms, versus 292.1 expected (SMR=0.92, 95% CI 0.81-1.04), 82 deaths from respiratory cancers versus 95.8 expected (SMR=0.86), and 15 deaths from bladder and urinary cancers versus 12.7 expected (SMR=1.18). None of these estimates were significant, and for none of the other cancer sites there was evidence of excess risk. Thus, epidemiological data allow excluding any appreciable risk of cancer--in particular of the respiratory and the urinary tract--in carbon electrode workers.     

Risk of second cancer in patients with hairy cell leukemia: long-term follow-up.

PURPOSE: The purpose of the present study was to assess the risk of second cancers in patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: We investigated the incidence of additional cancers in those patients registered in the nationwide registry of the Italian Cooperative Group for the Study of HCL, asking the cooperating centers for additional information on initial and subsequent therapies and on time and type of second malignancies, if they developed. Here we report the final results of this survey, consisting of 54 cases of second malignancies (excluding nine cases of epithelial skin cancer) which developed in 54 patients of 1,022 with adequate follow-up. RESULTS: The cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively. The incidence of second malignancies was not significantly higher than the expected rate (standardized incidence ratio [SIR], 1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of non-Hodgkin's lymphoma in the entire cohort was 5.3 (95% CI, 1.9 to 11.5). Second malignancies occurred in eight (4.7%) of 386 patients who never received interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line therapy. These differences were not statistically significant. Analysis of the separate calendar periods did not reveal any particular trends with respect to variations in SIR. CONCLUSION: The present study does not support the suspicion that patients with HCL are at increased risk of additional second malignancies, although the incidence of lymphoid neoplasms was significantly higher than expected. In addition, our data indicate that IFN therapy did not exert an oncogenic effect in such patients.     

Recent Developments in Nongastric Mucosa-Associated Lymphoid Tissue Lymphoma

Guidelines and algorithms for the management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma have been developed in the recent past, but the situation regarding nongastric MALT lymphomas is much more complicated. Owing to the heterogeneity of MALT lymphomas arising in various organs, different approaches to treatment have been applied, mostly in an uncontrolled fashion. In the recent past, for example, attempts to use antibiotic therapy in managing ocular adnexal MALT lymphomas have been reported, with response rates varying between 0% and 60% with the use of doxycycline or, more rarely, clarithromycin. Currently, antibiotic therapy remains experimental, with conflicting data and apparent geographic variations. In addition, there is no clear consensus whether radiation or systemic therapy is more effective in MALT lymphomas at different locations, including the lung and the ocular adnexa. This review highlights and briefly discusses some recent developments in the management of nongastric MALT lymphomas.     

Second malignant neoplasms after treatment for Hodgkin's disease in childhood or adolescence.

PURPOSE: To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin's disease diagnosed in children and adolescents. PATIENTS AND METHODS: One hundred eighty-two consecutive, previously untreated patients with Hodgkin's disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence. RESULTS: Twenty-eight patients developed an SMN at a mean of 14.93 +/- 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin's disease. The cumulative percentage of patients who developed an SMN was 26.27 +/- 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin's lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results. CONCLUSION: Successfully treated children and adolescents with Hodgkin's disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.     

Cancer risk among patients with cystic fibrosis and their first‐degree relatives

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population‐based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first‐degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1–4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow‐up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk. © 2009 UICC     

Nongastric mucosa-associated lymphoid tissue lymphomas

Nongastric mucosa-associated lymphoid tissue (MALT)-derived lymphomas arise from various extranodal locations and are usually related to a particular pathogenesis with a possible external (environmental or autoimmune) event inducing the disease. We reviewed 165 patients with nongastric MALT lymphoma among the 243 patients with MALT lymphoma in our database and reviewed reports in the literature to analyze the clinical features of nongastric MALT lymphomas. The site of clinical presentation was related to the lymphoma location and was usually indolent. Dissemination of the disease at diagnosis was noticed in 48% of cases because of the involvement of multiple mucosal sites (48%) or because of a nonmucosal site involvement such as bone marrow, spleen, or liver (52%). With a median follow-up of 4 years, the estimated 5-year overall survival and 5-year freedom-from-progression rates were 89% and 50%, respectively, without any difference between patients with localized or disseminated disease or among different locations. Treatment recommendations for localized disease are based on surgery, local therapy, or chlorambucil. For disseminated disease, treatment recommendations include chemotherapy with fludarabine or chlorambucil or chemotherapy with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) in cases of large tumor mass     

Second primary neoplasms following non-Hodgkin's lymphoma in New South Wales, Australia

The incidence of non-Hodgkin's lymphoma (NHL) has been increasing rapidly over the last three decades. The reasons for this trend are not known although increasing exposure to sunlight has been postulated. We used data from the New South Wales Central Cancer Registry to analyse second primary neoplasms following NHL diagnosed between 1972 and 1995, to identify possible common causal agents. A total of 12,452 patients contributed 54,308 person-years of follow-up during which time there were 705 second primary neoplasms compared to 592.99 expected (standardized incidence ratio (SIR = 1.19, 95% confidence interval (CI) 1.10-1.28). There were excesses of melanomas of skin (SIR = 2.38, 95% CI 1.92-2.91), lip cancer (SIR = 2.74, 95% CI 1.59-4.38), tongue cancer (SIR = 2.53, 95% CI 1.09-4.99) and bladder cancer (SIR = 1.64, 95% CI 1.19-2.21). There was also over a threefold excess in soft tissue sarcomas (SIR = 3.61, 95% CI 1.80-6.45) and in thyroid cancer (SIR = 3.42, 95% CI 1.56-6.49). The SIR for myeloid leukaemia was 0.78 (95% CI 0.28-1.69). The increases in melanoma of the skin and cancer of the lip and tongue among patients with NHL strongly suggest sunlight exposure as a shared causal agent. The increase in soft tissue sarcomas might be due to shared effects of exposure to chemicals such as phenoxy acid herbicides. The increases in bladder and thyroid cancers are likely to be explained by effects of treatment for NHL. We did not find a chemotherapy related increased risk of myeloid leukaemia among NHL patients.     

New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors.

PURPOSE: To determine the incidence and risk factors for the development of new malignancies occurring after stem-cell transplantation (SCT). PATIENTS: Between January 1, 1974, and March 31, 2001, 3,372 patients underwent SCT at the University of Minnesota. From these transplants, 147 posttransplant malignancies (PTMs) were identified in 137 patients. RESULTS: Excluding nonmelanoma skin cancers (n = 19) and carcinoma-in-situ (n = 5), the remaining 123 cases represented an 8.1-fold (95% confidence interval [CI], 6.7 to 9.6) increased risk of a PTM, an excess risk of 102.7 cases/10,000 persons/yr (age and sex adjusted). This includes a significantly elevated risk for developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML; standardized incidence ratio [SIR] = 300; 95% CI, 210 to 406), non-Hodgkin's lymphoma including posttransplant lymphoproliferative disorder (PTLD; SIR = 54.3; 95% CI, 39.5 to 41.1), Hodgkin's disease (SIR = 14.8; 95% CI, 3.9 to 32.9), or solid tumors overall (SIR = 2.8; CI, 2.0 to 3.7) and in specific for melanoma, brain, and oral cavity tumors. The cumulative incidence for the development of any PTM was 6.9% (95% CI, 5.2 to 8.6) at 20 years post-SCT. For PTLD (n = 43), the cumulative incidence plateaued at 1.4% (95% CI, 1.0 to 1.8) by 10 years post-SCT. For MDS or AML, the cumulative incidence plateaued at 1.4% (95% CI, 0.9 to 1.9) by 10 years post-SCT. The cumulative incidence of developing a solid tumor did not plateau and was 3.8% (95% CI, 2.2 to 5.4) at 20 years post-SCT. CONCLUSION: These data reveal that the risk of PTMs, especially solid tumors, continues to increase even 20 years after transplant, necessitating long-term close follow-up for these patients.     

Detection rate of fluorine‐18‐fluorodeoxyglucose positron emission tomography in patients with marginal zone lymphoma of MALT type: a meta‐analysis

The aim of this article is to meta‐analyse published data about the detection rate (DR) of fluorine‐18‐fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the evaluation of patients with marginal zone lymphoma of the mucosa‐associated lymphoid tissue (MALT). A comprehensive literature search of studies published through February 2014 was performed. Pooled DR of ¹⁸F‐FDG PET or PET/CT including 95% confidence intervals (95% CI) was calculated on a per‐patient‐based analysis. Twenty studies including 376 patients with MALT lymphoma were selected. The pooled DR of ¹⁸F‐FDG PET or PET/CT was 71% (95% CI: 61–80%). A significant difference between the DR of PET/CT (69%; 95% CI: 61–80%) and that of PET alone (73%; 95% CI: 60–84%) was not demonstrated. A better DR of ¹⁸F‐FDG PET or PET/CT in bronchial (94%; 95% CI: 85–99%) and head‐and‐neck (90%; 95% CI: 78–98%) MALT lymphomas compared with gastric (62%; 95% CI: 46–77%) and ocular (49%; 95% CI: 36–63%) MALT lymphomas was found. This meta‐analysis demonstrates that MALT lymphoma is an ¹⁸F‐FDG‐avid tumour in most of the cases, suggesting a potential clinical role of ¹⁸F‐FDG PET or PET/CT in the initial evaluation of these patients. In particular, the DR of ¹⁸F‐FDG PET or PET/CT is related to the primary site of the MALT lymphoma. Copyright © 2014 John Wiley & Sons, Ltd.     

Cancer risk among patients with condylomata acuminata

Condylomata acuminata have been shown to increase the risk of anogenital cancers. However, previous studies have been of limited sample size and/or short follow-up duration, which prevent precise estimates of long-term excess risk, especially for specific cancer sites. We estimated the risk of specific cancers in a large cohort of hospitalized patients with condylomata acuminata, as recorded in the Swedish Inpatient Register between 1965 and 1999. Altogether, 10,971 patients (1,685 men and 9,286 women) were followed through 1999 for a median of 13 years. The standardized incidence ratio (SIR)--the ratio of the observed number of cancers to the number expected on the basis of the incidence in the Swedish population at large--was used as a measure of relative risk. After excluding the first-year of follow-up, we observed 43 cases of anogenital cancer in women, and 7 cases in men. Risks were elevated for cancers of the vulva (N = 13, SIR = 10.2, 95% confidence interval (CI) = 5.4-17.4), vagina (N = 4, SIR = 12.0, 95% CI = 3.3-30.7) and penis (N = 5, SIR = 21.9, 95% CI = 7.1-51.2). There was a moderate excess risk of cervical cancer in situ (N = 259, SIR = 1.9, 95% CI = 1.7-2.1), but not invasive cervical cancer. Excess risks of esophageal, buccal cavity, nonmelanoma skin, lung and bladder cancers, and Hodgkin and non-Hodgkin lymphoma, were also observed in both men and women. In conclusion, condylomata acuminata are strongly associated with increased risk of cancers of the vulva, vagina, penis and anus, as well as some nonanogenital malignancies, but not invasive cervical cancer.     

Is there an increased rate of additional malignancies in patients with mantle cell lymphoma?

PURPOSE: To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). PATIENTS AND METHODS: A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. RESULTS: These patients were followed for a median time of 26 months, and a total of 32 (21%) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 11 following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P <0.0001]. Of the 21 malignancies diagnosed prior to MCL, 16 were invasive and five non-invasive. There were a total of 10 urologic malignancies occurring before or after the diagnosis of MCL was established. CONCLUSIONS: Our findings suggest that there is an increased incidence of second malignancies in patients with MCL. In addition, the high number of cases with urinary tract cancer in our series may substantiate prior reports describing a possible association between lymphoma and urologic malignancies.     

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.     

Reduced incidence of second solid tumors in survivors of childhood Hodgkin's lymphoma treated without radiation therapy

BackgroundWe assessed the risk of developing second malignancies in children treated for Hodgkin's lymphoma (HL), the majority of whom received chemotherapy only.Patients and methodsThe development of second malignancies in children with HL, treated between 1960 and 1999, was assessed. Results were obtained by both chart review and linkage with a centralized cancer registry. Tumor incidence was compared for patients treated with and without radiotherapy (RT) and with the general population. Risk factors for developing second tumors were assessed by multivariate analysis.ResultsOf 142 childhood HL patients, 63 had received RT and 79 had not. Overall survival was similar for both groups. Fourteen patients developed second solid tumors, 12 who had received RT and 2 treated with chemotherapy only (P <0.001), with a 30-year cumulative incidence of 24.7% [95% confidence interval (CI) 7.27–47.4] and 5.8% (95% CI 0–58.9), respectively (P = 0.01). The standardized incidence ratio for second solid tumors was 236 (95% CI 112.2–359.0) versus 43.6 (95% CI 0–103.9), respectively. Multivariate analysis showed treatment with RT was the only significant risks factor for developing second solid tumors.ConclusionsChildren with HL without RT have a substantially lower incidence of second tumors than those treated with RT.