Cumulative Incidence Of Second Cancer Research Articles

Long-term second primary cancer risk in adolescent and young adult (15-39 years) cancer survivors: a population-based study in the Netherlands between 1989 and 2018

Few studies have comprehensively investigated the long-term second cancer risk among adolescent and young adult (AYA, aged 15-39 years) cancer survivors. This study investigated the long-term second cancer risk by including the full range of first and second cancer combinations with at least 10 observations in the Netherlands between 1989 and2018. First and second primary cancer data of all 6-month AYA cancer survivors were obtained from the nationwide population-based Netherlands Cancer Registry. Excess cancer risk compared to the general population was assessed with standardized incidence ratio (SIR) and absolute excess risk (AER) statistics up to 25 years after diagnosis. Cumulative incidences were estimated, using death as a competing risk factor. Analyses were carried out with and without applying multiple cancer rules. The cohort included 99 502 AYA cancer survivors. Male survivors had a 2-fold higher risk of developing any cancer compared to the general population, whereas this was around 1.3-fold in females. AERs were 17.5 and 10.1 per 10 000 person-years for males and females. The long-term excess risk of cancer was significantly higher for most first and second primary cancer combinations, but comparable and lower risk estimates were also observed. Application of the multiple cancer rules resulted in a noticeable risk underestimation in melanoma, testicular, and breast cancer survivors. Risk outcomes remained similar in most cases otherwise. The cumulative incidence of second cancer overall increased over time up to 8.9% in males and 10.3% in females at 25 years' follow-up. Highest long-term cumulative incidences were observed among lymphoma survivors (13.3% males and 18.9% females). AYA cancer survivors have a higher cancer risk compared to the general population for most cancers up to 25 years after their initial cancer diagnosis. Additional studies that investigate risk factors for the specific cancer type combinations are needed to develop personalized follow-up strategies.

Outcomes of childhood, adolescent, and young adult cancer survivors (CAYACS) with solid organ transplants: A population-based study.

10056 Background: Organ toxicity requiring solid organ transplant (SOT) is a rare but serious effect of cancer treatment. Given restricted donor organ supply, teams must assess CAYACS requiring SOT in relation to potential recipients with non-malignant indications; decisions are limited by scant long-term outcome data. We compared long-term outcomes for CAYACS requiring SOT with other SOT recipients. Methods: All Ontario, Canada children < 18 years at cancer diagnosed 1986-2021 at pediatric centres, and AYA aged 15-21 diagnosed at adult centres for acute leukemia, lymphoma, sarcoma, or testicular cancer between 1992-2012 were identified using population-based clinical databases. Patients with SOT prior to their primary cancer diagnosis were excluded. SOT was identified through linkage to healthcare databases; patients were matched 1:2 to non-malignant SOT recipients by sex, SOT year and type, and birth year. Post-SOT outcomes including overall survival (OS) and post SOT cancers were compared between CAYACS and SOT controls. Results: Among 16,533 CAYA with cancer, 85 received SOT: 46 liver, 18 kidney, 11 lung, and 10 heart. Among liver recipients, 33 (71.7%) were for primary cancer treatment (e.g. hepatoblastoma) vs. 13 (28.3%) for organ toxicity. Median age at original cancer diagnosis was 4 years [interquartile range (IQR) 1-13] and at SOT was 13 (IQR 3-20). CAYACS with SOT as treatment for long-term toxicity (liver subset plus all renal, lung, heart, N = 52) had a median time from cancer diagnosis to SOT of 9 years (IQR 4-16) and experienced lower 10-year OS from time of SOT [67.7%, 95th confidence interval (95CI) 50.8-79.9] vs. SOT matched controls [86.0% (74.8-92.5); hazard ratio (HR) 3.9; 95CI 1.6-9.7; p = 0.003]. When stratified by SOT type, similar trends were seen but were only statistically significant among lung SOT recipients (Table). The 5-year cumulative incidence of primary cancer relapse from time of SOT among those who received liver SOT for primary cancer therapy was 15.9% (95CI 5.6-30.8). Among CAYACS who require SOT following organ toxicity, 10-year cumulative incidence of second cancers was 8.6%±4.2%; this was similar to the incidence of first cancer among SOT controls (6.4%±2.6%; HR 1.6, 95CI 0.6-4.0; p = 0.34). Conclusions: Though CAYACS requiring SOT have inferior survival compared to other SOT patients, the majority achieve long-term cancer-free survival. These data can inform discussions on the suitability of CAYACS for SOT. [Table: see text]

Long-Term Follow-up of Bendamustine Plus Rituximab Regimen in 69 Treatment Naïve (TN) Patients with Waldenström Macroglobulinemia, a Study on Behalf of the French Innovative Leukemia Organization (FILO)

Background Waldenström macroglobulinemia (WM) is a rare hematological malignancy characterized by the accumulation of IgM-secreting clonal lymphoma cells with a lymphoplasmacytic morphological differentiation. Recently, BTK inhibition has emerged as a promising therapeutic strategy in WM (Buske, JCO 2022; Tam, Blood 2020). However, in real life, a large part of patients(pts) continue to be treated by chemoimmunotherapy (Buske, Lancet Hematol2018) including bendamustine (B)-rituximab (R) in salvage (Tedeschi , Leukemia Lymphoma 2015) or first line MW (Treon, ASH2016). We have previously reported a series of 69 WM pts treated by BR (Laribi, BJH 2018) and demonstrated that this regimen is efficient. However, the follow-up was relatively short and some questions remained unresolved in terms of long-range response and second cancer occurrence. Here we report results of this series with a longer follow-up. Methods Sixty-nine symptomatic previously untreated pts with WM diagnostic criteria according to the second WM Workshop recommendations were enrolled in this retrospective multi-center study between January 2013 and December 2017 in 13 French centers. MYD88L265P and CXCR4 mutations were searched using qPCR and or next generation sequencing. Del(17p) and/or TP53 mutation were investigated in 34 pts. All pts received a BR regimen consisting of 375 mg/m2 of R on day 1 and 90 mg/m2 of B on days 1 and 2, repeated every 4 weeks, with a maximum of 6 cycles. Cumulative incidence of secondary malignancies and high-grade lymphomas were computed, considering death free of malignancies as a competing event. Event-free survival (EFS), time to next treatment (TNT), progression-free survival (PFS) and overall survival (OS) were plotted using the log rank test and Kaplan-Meier graphical comparison. Results Pts median age was 69 years old (yo; range 45-88) at WM diagnosis and 71 yo (range 46-88) at therapy initiation. MYD88 and CXCR4 mutations were present in 45/51 (88%) and 11/44 (25%) of pts, respectively. A complex karyotype was disclosed in 6/44 (14%) pts, and 1/34 (3%) had TP53 alteration. According to the IPSSMW score, 14 (22%) pts were low risk, 32(46%) intermediate, and 32 (46%) high risk. Using consensus response criteria, the overall response rate was 97% (very good partial response [VGPR] with negative immunofixation 19%, VGPR 37%, PR40%, MR 1%) and the major response rate was 96%. Cumulative incidence of VGPR or better was 47.8%, 53.6%, 55%, and 56% at 6, 12, 18, and 24 months, respectively. After a median observation time of 68.5 months (range 23.13-106) post BR, the median OS was not reached (83-NR) , and the median PFS was 82 months (75-NR). Median OS for pts with mutated or WT MYD88 was NR and 72.8 months, respectively (p=0.046). Median OS for pts with mutated or WT CXCR4 was 70.2 months and NR, respectively (p=0.64). Median OS related to disease or treatment was not reached, while median OS related to other causes was 106 months. Sixteen (23.2%) pts relapsed. Fourteen received second line therapy and 2 supportive care. Eight patients received ibrutinib, and 6 chemo-immunotherapy. TNT was 31.55 months (range 2.66-82.43). Median PFS after a second line of treatment (PFS2) was 45 (9.13-NR) or 21 months (range 9.13-NR), for pts receiving ibrutinib or not. Eleven pts developed a second cancer: 9 solid tumors (2 pancreatic, 2 gastric, 1colic, 1 pulmonary, 1 breast, 1 cutaneous), and 2 treatment-related myeloid neoplasms (TRMN). Median EFS, defined as occurrence of death, relapse or second cancer was 82 months (61-NR). The cumulative incidence of second cancer was 2.90%, 5.80%, 10.49%, and 17.6% at 12, 24, 48, and 96 months, respectively (figure 1). Univariate analyses on OS disclosed statistically significant differences for age at diagnosis (p=0.001), age at first therapy (p <0.001), IgM>70g/L (p: 0.018), complex karyotype (p=0.037), and high risk IPSSMW (p<0.01). In multivariate analysis, only IPSSMW remained statistically significant (p<0.001) (table1). Univariate analyses on PFS only singled out age at diagnosis (p=0.03) or at first therapy (p=0.049) as statistically significant. Mutated MYD88 or CXCR4 did not impact OS nor PFS. Conclusion This study demonstrates that the BR regimen is efficient in treatment naïve WM pts, yielding long-term responses. The occurrence of secondary cancers, including TRMN, should be closely monitored in these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population-based study.

To investigate the incidence of second primary cancers in people diagnosed with cancer during childhood. Retrospective, population-based study; analysis of Australian Childhood Cancer Registry data. People alive at least two months after being diagnosed before the age of 15 years with a primary cancer, 1983-2013, followed until 31 December 2015 (2-33 years' follow-up). Risks of second primary cancer compared with the general population, expressed as standardised incidence ratios (SIRs). Among 18230 people diagnosed with cancer during childhood, 388 (2%) were later diagnosed with second primary cancers; the estimated 30-year cumulative incidence of second cancers was 4.4% (95% CI, 3.8-5.0%). The risk of a new primary cancer was five times as high as for the general population (SIR, 5.13; 95% CI, 4.65-5.67). Relative risk of a second primary cancer was greatest for people who had childhood rhabdomyosarcoma (SIR, 19.9; 95% CI, 14.4-27.6). Relative risk was particularly high for children who had undergone both chemotherapy and radiotherapy (SIR, 9.80; 95% CI, 8.35-11.5). Relative risk peaked during the 5 years following the first diagnosis (2 to less than 5 years: SIR, 10.3; 95% CI, 8.20-13.0), but was still significant at 20-33 years (SIR, 2.58; 95% CI, 2.02-3.30). The most frequent second primary cancers were thyroid carcinomas (65 of 388, 17%) and acute myeloid leukaemias (57, 15%). Survivors of childhood cancer remain at increased risk of a second primary cancer well into adulthood. As the late effects of cancer treatment probably contribute to this risk, treatments need to be refined and their toxicity reduced, without reducing their benefit for survival.

Second Cancers in Adults with Acute Promyelocytic Leukemia (APL) Treated with or without Arsenic Trioxide (ATO): A SEER-Medicare Analysis

Background: ATO was approved by the U.S. Food and Drug Administration in 2000 for treatment of patients with relapsed/refractory APL and in 2018 in combination with all-trans retinoic acid (ATRA) for adults with newly-diagnosed low-risk APL. ATRA and ATO combinations result in long-term remissions in most patients with APL (Lo-Coco et al. NEJM 2013, Burnett et al. Lancet Oncol 2015). However, epidemiologic studies have shown associations between exposure to inorganic arsenic and development of skin, lung, bladder, and potentially liver, kidney, and prostate cancers (IARC 2004). The prescribing information for ATO includes a warning for carcinogenesis, with advice to monitor patients for development of second primary malignancies. Retrospective cohort analyses of second cancers in APL patients treated with ATO have been performed, finding incidence rates of 1-5% (Eghtedar et al. Leuk Lymphoma 2015, Au et al. Leuk Res 2007, Zhu et al. Blood 2016). We sought to perform an exploratory population-based analysis of second cancers in adults with APL treated with ATO compared to those treated with other systemic APL therapies without ATO using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Methods: Using SEER-Medicare linked data, we identified APL patients diagnosed from January 1, 2006 to December 31, 2015. Patients whose first SEER cancer diagnosis was APL, who were continuously enrolled in Medicare Parts A, B, &amp; D from the month of their APL diagnosis, and who received treatment with ≥ 1 systemic APL therapy within 1 year of diagnosis were included. Patients were followed from their first month of treatment group-defining APL therapy (ATO or non-ATO containing) until disenrollment from Medicare Parts A, B, or D, end of study period, or death. We determined the cumulative incidence of SEER-confirmed second cancers and overall survival (OS) according to whether patients were treated with or without ATO using the Kaplan-Meier method. We used a multivariate Cox proportional hazards model to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of cumulative incidence of second cancers and OS adjusted for relevant covariates of age, sex, and year of diagnosis. Results: We identified 1,442 APL cases, with 1,179 having APL as their first cancer diagnosis, of which 246 were enrolled in Medicare Parts A, B, and D. Of these, 64 received ATO and 60 received systemic APL therapy without ATO within 1 year of diagnosis. Characteristics, follow-up, and second malignancies for these cohorts are presented in the Table. Absolute incidence rates of second cancer were 3.4 per 1000 person-months compared to 1.4 per 1000 person-months in patients treated with and without ATO, respectively, and cumulative incidence rates at 24 months were 9.9% and 6.0%, respectively (p=0.20) (Figure 1). Mortality rates were 1.9 per 1000 person-months compared to 5.1 per 1000 person-months in patients treated with and without ATO, respectively, and OS rates at 24 months were 90.8% and 81.5%, respectively (p=0.10) (Figure 2). After adjusting for relevant covariates, HR for cumulative incidence of second malignancies in patients treated with ATO was 1.27 (95% CI 0.29-5.49; p=0.75) and for OS was 0.46 (95% CI 0.16-1.29; p=0.14) compared to APL therapy without ATO. Conclusions: This exploratory analysis revealed a high incidence of second malignancies in APL patients treated with ATO, although the risk was not significantly increased compared to patients who received other APL therapies. Most second malignancies following ATO were solid tumors, in line with prior epidemiologic studies of inorganic arsenic exposures. Despite the occurrence of second malignancies, there was a tendency towards longer OS in patients treated with ATO. Given the small sample size, short follow-up, potential selection and immortal time bias, and unaccounted for differences between comparator groups, firm conclusions cannot be inferred. However, the nearly 10% cumulative incidence of second malignancies at 24 months follow-up in Medicare patients with APL treated with ATO suggests the need for close monitoring for second malignancies following ATO therapy. Further prospective research into second malignancies following ATO is needed. Disclosures No relevant conflicts of interest to declare.

Waldenström Macroglobulinemia in Young Patients Treated in the Modern Era: A Multi-Institutional Italian Study

Background. Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma typical of the elderly population, with a median age at diagnosis of 65-70 years and median overall survival of approximately 10 years. Age is the most important prognostic factor in WM, and unrelated mortality significantly impacts survival in elderly patients. The past two decades have witnessed important treatment advances in WM, with the introduction of anti-CD20 monoclonal antibodies in the early 2000s and of ibrutinib in more recent years. Less than 10% of WM patients are diagnosed at young age, and few studies have addressed their characteristics and outcome in the era of immunotherapy and targeted therapies. Here we report the presenting features, treatment and outcome of WM patients younger than 55 years diagnosed in 12 Hematologic Centers across Italy between 2000 and 2018. Patients and Methods. Diagnostic criteria were those established during the second International Workshop on WM (Owen et al, 2003) and were retrospectively applied to patients diagnosed before 2003. The overall survival (OS) observed in the study cohort was compared with the expected survival of the general Italian population matched by sex, age and calendar year. The expected survival estimates were derived from Italian life tables (Istituto Nazionale di Statistica, ISTAT). Results. The median age of patients included in the study was 50 years (interquartile range, IQR: 46-52). Their clinical characteristics at diagnosis are reported in Table 1. With a median follow-up of 5.6 years (IQR 3.1-9.1), 76 of 129 patients (59%) have been treated, at diagnosis (n=31, 41%) or after initial observation (n=45, 59%). The median treatment-free survival was 39 months. According to ISS-WM prognostic score, 58% were classified as low risk, 30% as intermediate risk and 12% as high risk. Frontline therapy included Rituximab in 71/76 patients (93%). Rituximab was associated with chemotherapy in 62 patients (82%), whereas 9 patients (12%) received a chemo-free induction. Five patients (7%) received chemotherapy only as first-line therapy (Table 2). The overall response rate (ORR) to induction therapy was 85%, including 39% CR+VGPR. Two patients received Rituximab maintenance for 2 years. The median progression-free survival (PFS) after first-line therapy was 76 months. Four of 76 patients (5%) received an autologous stem cell transplantation at relapse/progression. Overall, 14/76 patients (18%) received ibrutinib as first (n=2) or as subsequent line of therapy (n=12). During follow-up, 4/76 patients (5%) developed a solid cancer (bladder n=2, breast n=1, prostate n=1) and 2 a second hematologic cancer (chronic myelomonocytic leukemia n=1, secondary MDS n=1). Using a competing-risk model, accounting for death from any cause as the competing event, the cumulative incidence of second cancers was 2% at 5 years and 5.8% at 10 years. Three patients have died, 2 due to WM and 1 due to acute myeloid leukemia. The 5-and 10-year OS from diagnosis were 99% and 96% respectively. In a time-dependent survival analysis, considering therapy as a time-dependent covariate, the OS of treated and untreated WM patients was not significantly different (P = 0.162) (Figure 1). Among treated patients, the OS was significantly shorter in high-risk patients as compared with low- and intermediate-risk patients (5-year OS 85.7% versus 100%, P=0.018) (Figure 2). The OS of young WM patients was not significantly reduced as compared with age-, sex- and calendar year- matched general population (P &amp;gt; 0.05) (Figure 3). Conclusions. The presenting features of young WM patients resemble those typically described in the elderly WM population. Among treated patients, more than half are low-risk according to ISS-WM, confirming age as the most important prognostic factor. More than 90% of patients received Rituximab as part of the upfront treatment, mainly in combination with chemotherapy. Ibrutinib seems to be preferred over autologous stem cell transplantation in the relapsed/refractory setting. The outcome of young WM patients treated in Italy in the contemporary era was excellent in terms of both PFS and OS, with a life expectancy not significantly reduced as compared with the general population. Figure 1 Disclosures Varettoni: Gilead: Other: travel expenses; Janssen: Consultancy; Roche: Consultancy; ABBVIE: Other: travel expenses. Tedeschi:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SUNESIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy. Benevolo:Novartis Pharmaceuticals: Consultancy. Del Fabro:Janssen: Consultancy. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor &amp; Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Arcaini:Gilead Sciences: Research Funding; Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.

Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History.

PurposeAlthough advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and to investigate the impact of family history.Patients and MethodsUsing the Swedish Family-Cancer Project Database, we identified 9,522 individuals with primary HL diagnosed between 1965 and 2012. We calculated standardized incidence ratios and cumulative incidence of second cancer in HL survivors and compared the standardized incidence ratios of lung, breast, colorectal, and all second cancers in HL survivors with and without a site-specific family history of cancer. Interactions between family history of cancer and HL treatment were evaluated under additive and multiplicative models.ResultsOverall, the risk of a second cancer in HL survivors was increased 2.39-fold (95% CI, 2.29 to 2.53). The 30-year cumulative incidence of breast cancer in women diagnosed with HL at younger than 35 years of age was 13.8%. We observed no significant difference in cancer risk over successive time periods. The risk of all second cancers was 1.3-fold higher for HL survivors with a first-degree relative with cancer (P < .001), with 3.3-fold, 2.1-fold, and 1.8-fold differences shown for lung, colorectal, and breast cancers, respectively. Moreover, a greater than additive interaction between family history of lung cancer and HL treatment was shown (P = .03).ConclusionHL survivorship is associated with a substantive risk of a second cancer. Notably, the risk is higher in individuals with a family history of cancer. This information should be used to inform risk-adapted therapy and to assist in screening to reduce long-term morbidity and mortality in patients with HL.

Impact of modern treatment strategies on second cancer incidence for patients with early stage seminoma: A population-based study in British Columbia.

423 Background: The purpose of this study is to examine the incidence of Second Cancers (SC) in patients with Stage I or II Seminoma treated in British Columbia (BC), and compare rates between patients managed with Radiation Therapy, Chemotherapy, or Active Surveillance. Methods: Consecutive patients with Stage I or II Seminoma (n = 1549, 21167 person years) diagnosed in British Columbia between 1984 and 2013 were identified from the BC Cancer Registry and included in this study. Patients were managed with Radiation Therapy (RT; n = 663), Chemotherapy (CT; n = 259) or Active Surveillance (AS; n = 624). Data was extracted from the registry and verified by individual patient chart review. Cumulative incidence rates were computed using competing risk analysis. Age and Sex Standardized Incidence Ratios (ASIR) were calculated (compared to the Canadian population). Results: After a median follow-up of 14 years (RT group: 21.5yrs, CT group: 10yrs, AS group: 8yrs), the 15 year Overall Survival was 91.4%. Only 15 patients died from progressive Seminoma, while 46 died from second cancers. A total of 115 patients developed SCs, and the cumulative incidence (CI) of SC, at 15 years, was: 5.9% for patients who received RT, 8.6% for those who had CT, and 4.9% for patients managed with AS. The higher CI for patients treated with CT, versus RT, was not statistically significant (p = 0.08). The ASIR for RT, CT and AS groups were 1.31 (95% Confidence Intervals: 0.92- 1.86), 2.57 (1.07- 6.15; p = 0.03), and 1.38 (0.75- 2.54), respectively. Patients who underwent treatment at ages 30-44yr and 45-59yr had a significantly higher ASIRs of 4.33 (2.1- 8.9; p &lt; 0.001) and 1.8 (1.16- 2.8; p = 0.008). ASIR was not significantly different when stratified by radiation dose, field types, or year of diagnosis. Conclusions: We found no statistically significant difference in the Cumulative Incidence of Second Cancers for patients treated with Radiation Therapy versus Chemotherapy in our patient population. Longer follow-up for the CT group is required to confirm trends evident in our analysis.

Risk of second cancer following radiotherapy for prostate cancer: a population-based analysis

BackgroundTo investigate the risk of second cancer and radiation induced second cancer following prostate cancer radiotherapy.MethodsWe compared men with radiotherapy only with those treated with radical prostatectomy only and those with radiotherapy after radical prostatectomy. Cumulative incidences of second cancers were calculated. Cox analyses were performed to identify determinants influencing second cancer incidence.ResultsNineteen thousand five hundred thirty eight patients were analyzed. Age and median follow-up differed significantly with radiotherapy only patients having the highest median age (70.3 years) and radical prostatectomy only patients the longest median follow-up (10.2 years). Ten-year cumulative incidence of second cancer was 15.9%, 13.2% and 10.5% for patients with radiotherapy only, radiotherapy after radical prostatectomy and radical prostatectomy only (p <0.0001). Increasing age and belonging to the radiotherapy only group were associated with a higher risk of second cancer—no significant increase was seen in radiotherapy after radical prostatectomy patients. A significantly higher rate of smoking related malignancies, like lung, bladder and non-melanoma skin cancer, was seen in radiotherapy only patients.ConclusionsNo clear increase in radiation induced second cancer was found in patients after radiotherapy for prostate cancer. Whereas the rate of second cancer was increased in radiotherapy only patients, no such increase was seen in patients with radiotherapy after radical prostatectomy. The increase of second cancer following radiotherapy only is highly likely to reflect advanced age and lifestyle habits and comorbidities.

Risk of Developing Second Cancers in Plasmacytoma in United States

Background: There is a well-known risk of developing multiple myeloma in plasmacytoma, especially in solitary bone tumors. However, the risk of other cancers is not clear. The aim of this study was to estimate the risk of second cancers in patients with plasmacytoma, as compared to general population, and patients with multiple myeloma.Methods: Surveillance, Epidemiology and End results (SEER) 18 dataset was queried to identify patients (ageResults: With a follow-up of 13,392 person-years, 331-second cancers were diagnosed in 2046 plasmacytoma survivors (1155 SPB and 891 extraosseous plasmacytoma). The risk of subsequent solid tumors was not higher compared to age and sex matched background population with a SIR of 1.02 (95 % CI .88-1.17 AER 2.23/10,000). The risk was higher for developing multiple myeloma (SIR 30.8 25-38 AER 67/10,000), leukemia (SIR 3.4, 95% CI; 2-5.2 AER 10/10,000) and non-Hodgkin’s lymphoma (NHL) (SIR 3.2, 95 % CI 2.1-4.7 AER 13.4/10,000) in "two-month" survivors of plasmacytoma as compared to general population. The risk of developing solid tumors was similar in SPB (SIR 1.07, 95% CI; .87-1.30 AER 9/10,000) and extraosseous (SIR .98, 95% CI; .77-1.19 AER -5/10,000) plasmacytoma. However the risk of transformation to multiple myeloma was 3.7 fold (hazard ratio 3.7, 95% CI; 2.2-6.3) (p<.001) higher in survivors of SPB (SIR 47.3 95% CI; 37-59 AER 103/10,000) than extraosseous plasmacytoma (SIR 13.6 95% CI; 8.3-21 AER 29/10,000). The mean duration for progression to multiple myeloma was significantly shorter for SPB; 348 months (95% CI; 340-356) vs 404 months (95% CI; 395-415) (p=<.001). The cumulative incidence of subsequent malignancies in the study cohort at 15 years was 24.5% (95% CI; 20.1-29.8) for SPB and 25.9 % (95% CI; 21.8-30.2) for extraosseous plasmacytoma. The risk of second malignancies in survivors of plasmacytoma was similar to survivors of multiple myeloma, and the cumulative incidence of second cancers did not differ according to the type of tumor (extraosseous, SPB, or multiple myeloma) (P=0.48). On a subgroup analysis risk did not change after excluding plasmacytoma survivors who developed multiple myeloma. The risk of NHL was significantly higher for patients with extraosseous plasmacytoma, with 42.3% (24.5-75.6%) of these patients developing NHL after 15 years. This stands in contrast to the 16.2% (11.6-20.1) of multiple myeloma survivors who subsequently developed NHL. The patients with SPB were at intermediate risk.Conclusion: The risk of second cancers in plasmacytoma survivors is not significantly different from the risks for second cancers in survivors of multiple myeloma. The extraosseous plasmacytoma survivors are at higher risk of developing NHL, which suggests further study. The risk of transformation into multiple myeloma, despite lower than solitary plasmacytoma of bone, is still very high (13.6 times than general population), and thus active surveillance by treating physicians is mandatory. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.

Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma

BackgroundSurvivors of Hodgkin’s lymphoma are at increased risk for treatment-related subsequent malignant neoplasms. The effect of less toxic treatments, introduced in the late 1980s, on the long-term risk of a second cancer remains unknown.MethodsWe enrolled 3905 persons in the Netherlands who had survived for at least 5 years after the initiation of treatment for Hodgkin’s lymphoma. Patients had received treatment between 1965 and 2000, when they were 15 to 50 years of age. We compared the risk of a second cancer among these patients with the risk that was expected on the basis of cancer incidence in the general population. Treatment-specific risks were compared within the cohort.ResultsWith a median follow-up of 19.1 years, 1055 second cancers were diagnosed in 908 patients, resulting in a standardized incidence ratio (SIR) of 4.6 (95% confidence interval [CI], 4.3 to 4.9) in the study cohort as compared with the general population. The risk was still elevated 35 years or more after treatment (SIR, 3.9; 95% CI, 2.8 to 5.4), and the cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95% CI, 45.4 to 51.5). The cumulative incidence of second solid cancers did not differ according to study period (1965–1976, 1977–1988, or 1989–2000) (P=0.71 for heterogeneity). Although the risk of breast cancer was lower among patients who were treated with supradiaphragmatic-field radiotherapy not including the axilla than among those who were exposed to mantle-field irradiation (hazard ratio, 0.37; 95% CI, 0.19 to 0.72), the risk of breast cancer was not lower among patients treated in the 1989–2000 study period than among those treated in the two earlier periods. A cumulative procarbazine dose of 4.3 g or more per square meter of body-surface area (which has been associated with premature menopause) was associated with a significantly lower risk of breast cancer (hazard ratio for the comparison with no chemotherapy, 0.57; 95% CI, 0.39 to 0.84) but a higher risk of gastrointestinal cancer (hazard ratio, 2.70; 95% CI, 1.69 to 4.30).ConclusionsThe risk of second solid cancers did not appear to be lower among patients treated in the most recent calendar period studied (1989–2000) than among those treated in earlier periods. The awareness of an increased risk of second cancer remains crucial for survivors of Hodgkin’s lymphoma. (Funded by the Dutch Cancer Society.)

Second cancers and late mortality in Australian children treated by allogeneic HSCT for haematological malignancy.

We examined risk of second cancer and late mortality in a population-based Australian cohort of 717 pediatric allogeneic stem cell transplant (HSCT) recipients treated for a malignant disease during 1982-2007. Record linkage with population-based death and cancer registries identified 17 second cancers at a median of 7.9 years post HSCT; thyroid cancer being the most common malignancy (n=8). The cumulative incidence of second cancer was 8.7% at follow-up, and second cancers occurred 20 times more often than in the general population (standardised incidence ratio 20.3, 95% confidence interval (CI)=12.6-32.7). Transplantation using radiation-based conditioning regimens was associated with increased second cancer risk. A total of 367 patients survived for at least 2 years post HSCT and of these 44 (12%) died at a median of 3.1 years after HSCT. Relapse was the most common cause of late mortality (n=32). The cumulative incidence of late mortality was 14.7%. The observed rate of late mortality was 36 times greater than in the matched general population (standardised mortality ratio 35.9, 95% CI=26.7-48.3). Recipients who relapsed or who had radiation-based conditioning regimens were at higher risk of late mortality. Second cancers and late mortality continue to be a risk for pediatric patients undergoing HSCT, and these results highlight the need for effective screening and survivorship programs.

Increased Risk for Second Primary Malignancies in Women with Breast Cancer Diagnosed at Young Age: A Population-Based Study in Taiwan

Studies conducted in Western countries have reported excess risks for second primary malignancies after breast cancer. However, there is little documentation of ethnic differences in these excess risks. Asian women are characterized by younger age at diagnosis of breast cancer, but very few reports are available on the incidences and risks for second primary cancers in this region. Using population-based data from the Taiwan National Cancer Registry (TNCR) for the period 1979 to 2003, we quantified standardized incidence ratios and cumulative incidence of second cancers among 53,783 women with initial diagnoses of breast cancer. Age-specific incidences showed peaks among women in their 40s, and 1,085 cases (2.02%) developed nonbreast second primary cancers. The risk for second cancers differs significantly according to age at diagnosis of breast cancer. In comparison with women diagnosed when >or=50 years (standardized incidence ratio, 0.96; 95% confidence interval; 0.89-1.04), there were significantly greater risks for bone, corpus uterine, ovarian, thyroid, esophageal, kidney and lung cancers, nonmelanoma skin cancer, and leukemia or lymphoma in women diagnosed when <50 years (standardized incidence ratio, 1.43; 95% confidence interval, 1.29-1.58). The survival probabilities differed between breast cancer patients with and without second cancers (P<0.001). After diagnosis of the second cancer, the median survival time was only 2.87 years. In conclusion, we confirmed that young age at diagnosis of breast cancer predicted a subsequently increased risk for second malignancies, and the second cancers indeed worsen survivorship in patients who survived breast cancer.

Second malignancies after treatment of diffuse large B-cell non-Hodgkin's lymphoma: a GISL cohort study

Improved treatment has increased the life expectancy of patients with non-Hodgkin's lymphoma, but few studies have addressed the issue of second cancer in patients treated for diffuse large B-cell lymphoma. The aims of this study were to determine the incidence and time free of second cancers in this subset of patients. We evaluated a cohort of 1280 patients with diffuse large B-cell lymphoma who were first treated between 1988 and 2003. We utilized the central database of the Gruppo Italiano Studio Linfomi, which includes data on demographics, clinical characteristics, laboratory parameters, treatment and follow-up of all patients with non-Hodgkin's lymphoma enrolled in clinical trials. After a median follow-up of 51 months, 48 patients had developed a second cancer: 13 hematologic malignancies and 35 solid tumors. The overall standardized incidence ratio in our cohort (with a median age of 58 years) matched that of the general Italian population. The incidence ratio of second tumors was age related, and the age groups 20-39 and 40-59 years showed an increased risk. Overall, the cumulative incidence of second cancer was 8.2% at 15 years. A multivariate analysis showed that older age at the time of diagnosis of lymphoma had a negative influence on the time free of second tumors. In our cohort, only young patients showed an increased incidence ratio of second malignancies, while the incidence ratio in patients aged over 59 years matched the incidence in the Italian general population. Demographics, baseline characteristics, laboratory parameters and treatment modalities did not have any significant impact on the incidence ratio of a second cancer.

The incidence and risk of second primary cancers in patients with nasopharyngeal carcinoma: a population-based study in Taiwan over a 25-year period (1979–2003)

BackgroundVery few reports are available on the incidence and risk of second primary cancers in nasopharyngeal carcinoma (NPC) cases, and most of these are single-institution reviews with relatively small case numbers and short follow-up. Patients and methodsA population-based study was conducted. We quantified standardized incidence ratios (SIRs) and cumulative incidence of second cancers among 23639 individuals with initial diagnoses of NPC. ResultsWe found a 24% increased risk of second cancers in NPC patients compared with the general population [SIR=1.24, 95% confidence interval 1.15–1.33]. Elevated SIRs were observed in the following second primary cancers: oral/pharyngeal, salivary gland, sarcoma, skin and leukemia/lymphoma. The cumulative incidence >10 years was 3.26%. The risk was higher in younger patients, especially those <40 years old. After diagnosis of second cancers, the median survival time was 1.7 years. ConclusionsThis is the largest population-based study to date from a high-incidence area. We found that NPC is associated with an increased risk of second malignancies, which had a negative impact on the survival of patients who survived NPC.

Second Cancers Occurring in Patients With Early Stage Non–Small-Cell Lung Cancer Treated With Chest Radiation Therapy Alone

To investigate the incidence of second cancers occurring in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with radiation therapy (RT) alone. Seventy-eight patients had been treated with conventionally fractionated (CF) RT (1982 to 1987), and 116 patients had been treated with hyperfractionated (Hfx) RT (1988 to 1993). Tumor doses were 60 Gy for CF and 69.6 Gy (1.2 Gy bid) for Hfx. A total of 26 patients developed second cancers. The cumulative incidence of second cancer was 21.8% (SE, 4.7%) at 5 years and 34.8% (SE, 6.7%) at 10 years. For second lung cancers, it was 6.0% (SE, 2.8%) at 5 years and 14.2% (SE, 5.2%) at 10 years, and for second nonlung cancers, it was 16.3% (SE, 4.2%) at 5 years and 22.2% (SE, 5.7%) at 10 years. The rate of developing second cancer per patient per year was 4.3% (95% confidence intervals [CI], 2.7% to 5.9%), with the rates being 1.4% (CI, 0.5% to 2.3%) for the second lung cancers and 2.8% (CI, 1.5% to 4.1%) for second nonlung cancers. The rate of developing second cancers during the first and second 5-year period after RT (0 to 5 and 5 to 10 years) was 4.3% (CI, 2.4% to 6.2%) and 4.2% (CI, 0.6% to 7.8%), respectively, for all cancers. These rates were 1.0% (CI, 0.1% to 1.9%) and 2.2% (CI, 0% to 4.6%), respectively, for second lung cancers, and 3.2% (CI, 1.6% to 4.8%) and 1.5% (CI, 0% to 3.6%), respectively, for second nonlung cancers. Long-term survivors after RT alone for early stage NSCLC carry the same risk of developing second cancer, either lung or nonlung, as their counterparts treated surgically when the results of this study are compared with those of the published literature.

Lumpectomy Compared with Lumpectomy and Radiation Therapy for the Treatment of Intraductal Breast Cancer

Women with ductal carcinoma in situ have been treated both by lumpectomy and by lumpectomy followed by radiation therapy, but the benefit of combined therapy is uncertain. A group of 818 women with ductal carcinoma in situ were randomly assigned to undergo lumpectomy or lumpectomy followed by breast irradiation (50 Gy). Sufficient tissue was removed that the margins of the resected specimens were histologically tumor-free. The mean duration of follow-up was 43 months (range, 11 to 86). The principal end point of the study was event-free survival, as defined by the presence of no new ipsilateral or contralateral breast cancers, regional or distant metastases, or other cancers and by no deaths from causes other than cancer. Five-year event-free survival was better in the women who received breast irradiation (84.4 percent, vs. 73.8 percent for the women treated by lumpectomy alone; P = 0.001). The improvement was due to a reduction in the occurrence of second ipsilateral breast cancers; the incidence of each of the other events was similar in the two groups. Of 391 women treated by lumpectomy alone, ipsilateral breast cancer developed in 64 (16.4 percent); it was noninvasive in 32 and invasive in the remaining 32. Of 399 women treated with lumpectomy and breast irradiation, ipsilateral breast cancer developed in 28 (7.0 percent) (noninvasive in 20 and invasive in 8). The five-year cumulative incidence of second cancers in the ipsilateral breast was reduced by irradiation from 10.4 percent to 7.5 percent for noninvasive cancers and from 10.5 percent to 2.9 percent for invasive cancers (P = 0.055 and P < 0.001, respectively). Breast irradiation after lumpectomy is more appropriate than lumpectomy alone for women with localized ductal carcinoma in situ.

Sex differences in risk of second malignant tumours after Hodgkin's disease in childhood

There have been reports of a high incidence of second malignant disorders in survivors of Hodgkin's disease. We studied the cumulative incidence of second tumours in 191 children, who were 16 years or younger at diagnosis, with stage IA-IVB Hodgkin's disease, treated at the Joint Center for Radiation Therapy, Boston, between 1969 and 1988.The 10-year actuarial survival was 89 (SE 2)%. The median follow-up time was 11 (range 3-21) years from diagnosis. 109 children were initially treated with radiotherapy alone, 61 received chemotherapy and radiotherapy, and 21 received chemotherapy alone. Second tumours arose in 15 patients 6-20 years after the diagnosis of Hodgkin's disease. The estimated cumulative incidence of second malignant disorders at 15 years was 12 (4)% overall. 10 of the second tumours arose among 66 female patients, compared with 5 among 125 male patients (cumulative incidence 24 [9] vs 5 [3]%). The relative risk of a second tumour for female compared with male patients was 4·5 (95% Cl 1·4-15·1; p=0·013). For male patients, the observed incidence of second tumours was 18 times that expected for the normal population (95% Cl 6-42), whereas for female patients it was 57 times that expected (27-105). 13 of the second malignant disorders were solid tumours, including 4 breast cancers.Thus, the risk of a child treated for Hodgkin's disease developing a second tumour is higher for girls than for boys. The cumulative incidence of second cancers increases from 10 years after treatment. These findings emphasise the importance of continued surveillance in patients treated for Hodgkin's disease.

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.