Incidence Of Second Malignancies Research Articles

Palifermin For Prevention Of Oral Mucositis Has No Negative Effect On Long-Term Outcome In Patients With Hematological Malignancies Undergoing HSCT - Long-Term Follow-Up To 15 Years

Background Palifermin has been shown to reduce the incidence and duration of severe oral mucositis in hematological stem cell transplantation (HSCT) recipients. A follow-up study was performed to rule out a potential long-term safety risk of palifermin use. Objectives to compare long-term disease outcome (overall survival, disease progression and incidence of secondary malignancies) between palifermin and placebo. Methods This is a long-term follow-up study of patients with hematological malignancies undergoing HSCT and treated with palifermin or placebo to prevent oral mucositis. The aim of the study was to detail any potential late complications due to palifermin exposure. Patients were enrolled between 1997-2003 into four randomized, placebo-controlled phase II/III studies conducted at 31 sites in Australia, Europe and the US. The survival outcomes were compared using hazard ratios (HRs) estimated with Cox model including the treatment group, baseline age, disease type (Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, leukemia), ECOG performance status, country and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with chi-squared test. Results A total of 672 patients were randomized to the parent studies (429 palifermin, 243 placebo) and 543 (345, 198) were enrolled to the long-term follow-up. The median follow-up time for subjects alive was 7.9 years (range 0.1-14.9) for palifermin and 8.8 (0.1-14.8) for placebo. No significant differences were seen for either overall survival (HR = 1.01; 95% confidence interval (CI) 0.78-1.31; p=0.921) or progression-free survival (HR=1.04; 95% CI 0.83-1.31; p=0.733). Secondary malignancies were reported by 13% (palifermin) vs. 11% (placebo) of the patients (p=0.477). The most common secondary malignancies were acute myeloid leukemia/myelodysplastic syndrome (5% vs. 5%) and skin cancers (2% vs. 2%). Conclusion The overall survival, progression-free survival, and the incidence of secondary malignancies were comparable between palifermin and placebo in patients undergoing HSCT. After a follow-up of up to 15 years, no negative effect of palifermin on long-term outcomes was observed. Disclosures: No relevant conflicts of interest to declare.

Changes In The Use Of Radiation Therapy Among Adolescents and Young Adults With Early Stage Classical Hodgkin Lymphoma: Implications For Survival and Risk Of Secondary Malignancies

BackgroundEarly stage classical Hodgkin lymphoma (HL) is a highly curable disease with the combined use of chemotherapy and radiation therapy (RT). There has been a recent trend to abandon RT, driven mostly by concerns of development of secondary malignancies (SMN). However, it is unknown whether the omission of RT in adolescents and young adults (AYA) with early stage HL affects survival and the risk of developing SMN. MethodsWe used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the overall survival (OS) and the risk of SMN among AYA with early stage HL treated or not with radiation therapy. Inclusion criterion was the diagnosis of stage I or II HL in the period of 1995-2010 as first malignant neoplasm among patients age 13 to 40 years. Patients with less than 6 months of follow up and patients with unknown use of RT were excluded. Follow up was updated to the end of 2012 (November 2012 submission). Cases were divided in two “eras”, 1995-2002 and 2003-2010, with the latter being expected to reflect changes in the use of RT. The impact of the era, RT, age, race, gender, and stage on survival were accessed utilizing multivariate analysis. Cumulative incidence of SMN among early stage HL survivors was calculated using a competing risk model, treating death from any cause in absence of SMN as the competing risk. ResultsA total of 5,336 early stage HL cases were included in the analysis with median follow up of 89 months (range 7-191). Median age of patients was 27 years, 2,459 (46%) were male, 1,327 (24.8%) had stage I, 512 (9.7%) had classical HL non otherwise specified, 4,231 (79.2%) had nodular sclerosing HL, 442 (8.3%), had mixed-cellularity HL, 130 (2.4%) had lymphocyte-rich HL, and 21 (0.4%) had lymphocyte depleted HL. Most patients were white (4,438; 83.2%), 513 (9.6%) black, 337 (6.4%) other ethnicity, and 44 (0.8%) unknown. There where 2,793 patients in the 1995-2002 era and 2,542 patients in the 2003-2010 era. Radiation was included in the initial treatment of 1,659 (59.4%) patients in the former and 1,351 (53%) patients in the latter era (P<0.001). Factors associated with use of RT were earlier era, white race and stage II HL. Within the 1995-2002 era, there was a trend towards better survival among patients treated with RT (5-year survival 95.0% vs. 93.6%, P=0.058). In the 2003-2010 cohort survival was superior among patients treated with RT (5-year survival 97.3% vs. 95.9%, P=0.008). In multivariate analysis, diagnosis of HL in the 1995-2002 era (HR=1.73, 95% C.I. 1.31-2.28, P < 0.001), black race (HR= 2.18, 95% C.I. 1.63-2.91, P <0.001), male sex (HR=1.55, 97% C.I. 1.24-1.93, P < 0.001), and omission of RT (HR=1.31, 95% C.I. 1.05-1.64, P=0.017) were associated with higher mortality. The cumulative incidence of SMN was not significantly different between patients treated or not with radiation, while the risk of death was higher among patients not treated with RT (Figure). [Display omitted] ConclusionThere has been a reduction in utilization of RT among AYA with early stage HL in the US. Omission of RT was associated with increased overall mortality but no reduction in incidence of SMN and should not be adopted outside clinical trials. Disclosures:No relevant conflicts of interest to declare.

Long-Term Outcome Of Adolescents and Young Adults (AYA) After Autologous Transplantation For Lymphoma; Single Center Experience With Bu-CY-VP16 Conditioning Therapy

Background Adolescents and young adults (AYA) with cancer have been designated as a vulnerable population by the National Cancer Institute. This group, defined by the ages of 16-39 years, has not enjoyed the same survival improvements over the past several decades as older and younger cohorts. Most of the AYA patients with lymphoma are curable, even in advanced stage. After first-line therapy, 15% to 20% do not respond to treatment and relapse. Busulfan based preparative regimens have been effective in ASCT for a Hodgkin lymphoma (HL) and non- Hodgkin lymphoma (NHL). This study aims to determine the long term outcomes among AYA patients with lymphoma who received Busulfan based regimen for ASCT. Study and patient characteristics This was a retrospective study for AYA patients (age 16-39) undergoing ASCT for lymphoma consolidation between Jan/2000 and Dec/2010 at Taussig’s Cancer Center. Patients were identified from our Bone Marrow Transplantation database. Most of the patients (98.6%) had received Bu-Cy-VP16. Briefly, Busufan (Bu) total dose was 14 mg/kg, Etoposide 60mg/kg and cyclophosphamide dose 120mg/kg. Busulfan was not targeted and it was administered orally or IV. Pre-transplant patient and transplant characteristics are presented in table-1 and table-2 respectively. Outcomes and results There were total 146 patients who received Bu-Cy-VP16 (80 HL, 66 NHL). The median age was 32 years (range, 16-39 years). Only 37 patients (25.3%) were in CR, 89 patients (61.0%) were PR and 20 patients (13.7%) had refractory disease. Most patients had at least 2 regimens of chemotherapy prior to ASCT. The regimen was well tolerated, with day 100 mortality 4.1% and non-relapse mortality 2.7%. With a median follow up of 6.2years, 5-year relapse-free survival (RFS) and overall survival (OS) were 46.6 % and 61.2%; 10-year RFS and OS were 44.6% and 55.7% (figures 1). Four patients developed secondary malignancy (2.7%); the secondary malignancy were: ALL at 1.7 yrs after transplant, AML at 2.3 yrs, MDS at 2.5 yrs. One patient developed lung carcinoma. Cumulative incidence of secondary malignancy at 10 years is 3% which is considerably less than 9% that we reported in our whole patient population who gets this regimen which could be attributed to age and also due to previous chemotherapy regimens. Prognostic factors for OS and RFS Worse ECOG performance status (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.13-2.28, P=0.009) and HL diagnosis (HR 1.78, CI 1.01-3.14, P=0.048) were the only significant risk factors for mortality in multivariable Cox analysis. Worse ECOG performance status (HR 1.53, CI 1.11-2.10, P=0.010 was the only prognostic factor for relapse/mortality (RFS). Conclusion The study confirms that Bu-Cy-VP16 is very well tolerated in AYA population with low 100-day NRM and very low incidence of secondary malignancy. Disclosures: Duong: Celgene: Honoraria, Research Funding. Hill:Celgene: Honoraria, Research Funding.

Lenalidomide and Dexamethasone Alone Is Equivalent To Lenalidomide and Dexamethasone With Autologous Stem Cell Transplant In Newly Diagnosed Multiple Myeloma: Interim Study Results Of a Randomized Trial

The current standard of care for patients with newly diagnosed multiple myeloma (MM) aged less than 65 years is high-dose chemotherapy combined with autologous stem cell transplantation (ASCT) based on improved progression free survival (PFS) and overall survival (OS) compared with conventional chemotherapy. The introduction of novel agents, for example lenalidomide and bortezomib over the last decade, has substantially improved MM outcomes providing similar response rates to ASCT. As a consequence, the role of upfront ASCT has become more controversial. Therefore, this randomized clinical trial aims to determine the role of upfront ASCT in patients with newly diagnosed MM patients receiving lenalidomide and low-dose dexamethasone as induction therapy.Patients enrolled into the study were aged ≥18 years with newly diagnosed MM, transplant eligible, and meeting CRAB criteria. Patients were randomized to receive 4 cycles of lenalidomide (25 mg days 1–21) plus low-dose dexamethasone (40 mg days 1, 8, 15, 22) followed by ASCT conditioned with 200 mg/m2 melphalan (Arm A; LD+ASCT) or 8 cycles of lenalidomide plus low-dose dexamethasone (Arm B; LD alone). Both groups received lenalidomide maintenance therapy 10-15 mg for up to 2 years. Patients in both treatment arms received stem cell collection after 4 cycles of lenalidomide plus dexamethasone if at least a partial response was achieved. Patients with stable disease or progressive disease (PD) went off study. The primary objective was to compare the best response between patients treated with lenalidomide plus dexamethasone followed by ASCT and patients treated with lenalidomide plus dexamethasone alone. Secondary objectives were to compare the duration of response (DOR), PFS, and OS between the two treatment arms and to evaluate the secondary malignancies in both arms.Fifty patients with newly diagnosed MM were randomized between February 2008 and May 2013, and 47 patients were eligible for evaluation in this interim analysis; 25 patients randomized to Arm A (LD+ASCT) and 22 patients randomized to Arm B (LD alone). Overall, patients had a median age of 61.6 years (range 48–75), 60% were male, 34% ISS Stage I, 49% ISS Stage II, 17% ISS Stage III. The data were analyzed according to the IMWG response criteria (Blood. 2011 May 5;117(18):4691-5). In an intention-to-treat analysis, there was a trend towards improved overall response rate (ORR) in patients receiving LD+ASCT (96%) compared with patients receiving LD alone (77%; p=0.08) (Table 1). After a median follow-up of 36.8 months (range 1.1–62.7), the median DOR was 13.9 months (95% confidence interval [CI] 4.0–34.1) in the LD+ASCT group compared with 21.2 months (95% CI 11.0–22.9) in the LD group. Overall, 18 patients have PD (10 patients in the LD+ASCT arm and 8 patients in LD arm), and 8 patients have died (4 patents in the LD+ASCT arm and 4 patients in the LD arm). Median PFS for LD+ASCT versus LD was 17.0 months (95% CI 15.5–not estimable) versus 25.2 months (95% CI 9.0–not estimable; p=0.94). Median OS for LD+ASCT versus LD was 57.6 months (95% CI 48.0–not estimable) versus not reached (p=0.94). Two patients in the LD alone arm developed a secondary malignancy, including 1 patient with myelodysplastic syndrome (MDS) 13 months after the start of therapy.This interim analysis of an ongoing randomized clinical study comparing lenalidomide plus low-dose dexamethasone induction with and without upfront ASCT in patients with newly diagnosed MM suggests that addition of ASCT resulted in a trend towards improved ORR. This did not result in a significant difference in terms of PFS or OS between the two treatment arms. In contrast there was a trend of better DOR in the LD alone arm. The data show that LD alone can achieve similar results as LD+ASCT, however careful interpretation is required due to the low patient number and relatively short follow-up. The incidence of secondary malignancy was low, including the development of 1 MDS. Disclosures:Schecter:Celgene: Honoraria, Speakers Bureau. Mapara:Celgene: Research Funding, RO1 Other. Lentzsch:Celgene: Research Funding.Table 1Best response and survivalBest response, n (%)Arm A (LD+ASCT) (n=25)Arm B (LD alone) (n=22)Stringent complete response1 (4.0)1 (4.6)Complete response4 (16.0)5 (22.7)Very good partial response8 (32.0)6 (27.3)Partial response11 (44.0)5 (22.7)Stable disease1 (4.0)5 (22.7)Progressive disease00Overall response rate24 (96.0)17 (77.3)

Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy

The leading cause of death among patients with hereditary retinoblastoma is second malignancy. Despite its high rate of efficacy, radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of nontarget tissue. The current study compared the risk of second malignancy in patients with retinoblastoma who were treated with photon and proton RT. A retrospective review was performed of patients with retinoblastoma who were treated with proton RT at the Massachusetts General Hospital or photon RT at Boston Children's Hospital between 1986 and 2011. A total of 86 patients were identified, 55 of whom received proton RT and 31 of whom received photon RT. Patients were followed for a median of 6.9 years (range, 1.0 years-24.4 years) in the proton cohort and 13.1 years (range, 1.4 years-23.9 years) in the photon cohort. The 10-year cumulative incidence of RT-induced or in-field second malignancies was significantly different between radiation modalities (proton vs photon: 0% vs 14%; P = .015). The 10-year cumulative incidence of all second malignancies was also different, although with borderline significance (5% vs 14%; P = .120). Retinoblastoma is highly responsive to radiation. The central objection to the use of RT, the risk of second malignancy, is based on studies of patients treated with antiquated, relatively nonconformal techniques. The current study is, to the authors' knowledge, the first to present a series of patients treated with the most conformal of the currently available external-beam RT modalities. Although longer follow-up is necessary, the preliminary data from the current study suggest that proton RT significantly lowers the risk of RT-induced malignancy.

Long-term survival in patients with germ cell testicular cancer: A population-based competing-risks regression analysis

Incidence of secondary malignancies and cardiovascular diseases among testicular germ cell tumor (TGCT) survivors is higher compared to the general population. We sought to describe the rates of other-cancer (OCM), non-cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT. Using the Surveillance, Epidemiology, and End Results (SEER) database, 31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates. Survival rates were stratified according to histology (seminoma vs. non-seminoma), median age (<34 vs. ≥34 years old), and disease stage (localized vs. regional vs. distant). Competing-risks Poisson regression methodologies were performed. For seminoma patients, the rates of CSM at 15 years increased with advancing stage (0.4-12.6%; P < 0.001), but varies little with age. In contrast, the rates of OCM (0.4-7.9%) and NCRM (2.9-8.9%) at 15 years increased with advancing stage and age (all P < 0.001). For non-seminoma patients, the 15-year CSM rates increased with advancing stage and age (1.9-24.4%; all P < 0.001). For the same time point, the rates of OCM (0.3-11.4%) and NCRM (2.4-8.0%) also increased with age and stage (all P ≤ 0.001). The risk of dying from secondary malignancies or other causes significantly increases with advancing stage and age at diagnosis among TGCT survivors. Such information can help provide patients and physicians with better screening strategies, follow-up protocols, and mental preparedness for such undesirable effects.

Decrease in the Incidence of Second Malignancies in Patients With Early-Stage Hodgkin Disease Treated in the Modern Radiotherapeutic Era

Decrease in the Incidence of Second Malignancies in Patients With Early-Stage Hodgkin Disease Treated in the Modern Radiotherapeutic Era

Time Trend of Multiple Myeloma and Associated Secondary Primary Malignancies in Asian Patients: A Taiwan Population–Based Study

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78–1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79–21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.

Risk of second malignancies in patients with gastric marginal zone lymphomas of mucosa associate lymphoid tissue (MALT)

It is controversial whether patients with gastric marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) have higher risk of second malignancies. The aim of this study was to define the risk of second malignancies in these patients. We analyzed prospective follow-up data of 146 consecutive patients with gastric MALT lymphoma treated at Aichi Cancer Center Hospital and compared the incidence of second malignancies with that in the general population. We calculated the standardized incidence ratio (SIR), using age- and sex-specific incidence rates from the Aichi Cancer Registry. The median follow-up period was 74 months. A total of 27 tumors occurred in 22 patients (15.1%), including 19 solid tumors. Of these, nine tumors were detected concomitantly with, and 18 tumors following, the diagnosis of gastric MALT lymphoma. Four patients had two second malignancies each. For the entire group, the SIR of an additional malignancy was 3.39 (95% confidence interval [CI] 2.11-4.66). An increased incidence of solid tumors (SIR 2.91 [1.60-4.22]) and hematologic malignancies (SIR 5.54 [1.70-9.38]) were seen. In addition, there was increased risk for development of second malignancies during follow up (SIR 2.26 [1.21-3.30]). Chemotherapy for treatment of MALT was an independent risk factor for second malignancies (age-sex adjusted hazard ratio 3.98 [1.47-10.79]. Compared with the general population, patients with gastric MALT lymphoma are at increased risk for second malignancies, including gastric cancer.

Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation

Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron in Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009). The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating.

Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience

Despite the well-defined role of autologous haematopoietic stem cell transplantation (autoHCT) in the treatment of patients with relapsed or refractory Hodgkin lymphoma (HL), relapse remains the main cause of transplant failure. We retrospectively evaluated long-term outcome and prognostic factors affecting survival of 132 patients with refractory (n = 89) or relapsed HL (n = 43) treated with autoHCT following modified BEAM. With a median follow-up of 68 months, the 10-year overall survival (OS) and progression-free survival (PFS) were 76 and 66 %, respectively. The 10-year cumulative incidence of second malignancies was 7 %. In multivariate analysis, age ≥45 years, more than one salvage regimens and disease status at transplant worse than CR were factors predictive for poor OS. In relapsed HL, age at transplant, response duration (<12 vs. ≥12 months) and the number of salvage regimens were independent predictors for PFS. In the refractory setting, disease status at autoHCT and the number of salvage regimens impacted PFS. The number of risk factors was inversely correlated with PFS in both relapsed and refractory HL (p = 0.003 and <0.001, respectively). The median PFS for patients with >1 risk factor in the relapsed and refractory setting was 5 and 11 months, respectively, in comparison with the median PFS not reached for patients with 0–1 risk factor in both settings. We conclude that high proportion of patients with relapsed/refractory HL can be cured with autoHCT. However, the presence of two or more risk factors helps to identify poor prognosis patients who may benefit from novel treatment strategies.

Plasmablastic lymphoma after standard-dose temozolomide for newly diagnosed glioblastoma

Secondary malignancies due to alkylating agents or topoisomerase II inhibitors are a concern in patients treated for primary brain tumors of the nervous system. Myelosuppression is the dose-limiting toxic effect of the alkylating agent temozolomide; reversible hematologic toxicity consisting mainly of thrombocytopenia is reported to occur in 7% of patients treated with concomitant radiotherapy and temozolomide and 14% with adjuvant temozolomide.1 However, the incidence of secondary malignancies and nonreversible hematologic disorders, such as myelodysplastic syndrome, are a rare complication of temozolomide.2

Definitive radiotherapy for T1 glottic squamous cell carcinoma: a 15-year Cruces University Hospital experience

To evaluate the treatment outcomes for T1 N0 glottic carcinoma after definitive radiotherapy. One hundred and seventeen patients treated with radical radiotherapy from 1990 to 2006 were retrospectively reviewed. The median follow-up duration for the entire group was 92 months (range 4-227). A median dose of 70 Gy (range 63-70 Gy) was administered. We determined the rates of local control (LC), regional control, overall survival (OS) and cause-specific survival (CSS) at 5, 10 and 15 years by Kaplan-Meier product-limit method. The Cox regression analysis was performed to identify significant prognostic factors for LC and survival. The incidence of secondary malignancies is also reported. The 5-, 10- and 15-year LC rates for the whole group were 84, 80.2 and 80.2 %, respectively. There were 20 local recurrences, of which 19 were salvaged with laryngectomy, giving an ultimate control rate of 90.6 %. The 5-/10-/15-year OS and CSS rates were 81.2 %/66.1 %/48.3 % and 90.6 %/90.6 %/90.6 %, respectively. None of the parameters analyzed exhibited a statistically significant relationship with LC. The age ≥65 years had a statistically significant effect on OS (but not in CSS), with a hazard ratio of 2.45 (95 % confidence interval 1.29-4.66; p = 0.006). During follow-up, 26 patients (22 %) developed a secondary malignancy. Only two patients (1.7 %) presented with severe toxicity (edema and mucositis). Radiotherapy alone offers a high likelihood of LC and an excellent CSS rate. In addition, the surgical approach for the salvage is a successful option.

Long-Term Outcomes Following Low-Dose Radioiodide Ablation for Differentiated Thyroid Cancer

Randomized trials show that low-dose (1.1 GBq [30 mCi]) radioiodide (RAI) has efficacy equivalent to high-dose RAI (3.7 GBq [100 mCi]) in thyroid remnant ablation (TRA) for differentiated thyroid cancer. Long-term follow-up is required to ensure detection of late recurrences and to confirm equivalence in terms of survival end points. However, median follow-up duration within randomized trials is currently limited. We studied 53 patients undergoing TRA for differentiated thyroid cancer with long-term follow-up in the Thyroid Unit of The Royal Marsden Hospital (Sutton, United Kingdom). Patients were treated with TRA using low-dose (1.1 GBq) RAI. Disease-free survival, overall survival, and the incidence of second malignancies were measured. Multivariable analysis was used to determine clinical risk factors for failure to achieve TRA after low-dose RAI. Median follow-up was 24 (range, 4-34) years. Low-dose RAI TRA was successful in 26 (49%) patients (successful ablation [SA] group), whereas 27 (51%) patients required further treatment (unsuccessful ablation [UA] group). Thirty-year disease-free survival was 92% in the SA group vs 87% in the UA group (P = .601). Thirty-year overall survival was 81% in the SA group vs 62% in the UA group (P = .154). Nine (17%) patients developed second malignancies (4 in the SA group and 5 in the UA group). Predictors of failure to achieve TRA with low-dose RAI were male sex and stage pT4 disease. There is no evidence from long-term follow-up of our cohort that treatment outcomes are compromised for patients that fail TRA with low-dose RAI and subsequently receive high-dose RAI.

Secondary malignancy in patients with sporadic neuroendocrine neoplasia

The incidence of neuroendocrine neoplasias (NENs), especially of the gastro-entero-pancreatic (GEP), system relatively increased over the past decades, as a result of advanced diagnostic tools, a better clinical awareness, and distinguished pathological diagnostic recognition. Previous reports hypothesized an increased risk for secondary malignancies in patients with NEN especially in GEP-NENs. The present study was designed to investigate the coincidence of NENs and secondary malignancies in a large patient collective. A retrospective analysis was performed on 161 patients (85 female and 76 male) with NEN of various origins. Clinical data of these patients, different classification systems (TNM/WHO), proliferations-based grading, and clinical follow-up were collected and analyzed. Out of 143 patients with a sporadic NEN, 15 (10.49 %) patients were identified with secondary malignant tumors. Median age at the time of the primary operation for NEN was 65 years, whereas the median age of initial diagnosis of associated tumors was 59 years. Mean follow-up time was 61 months. The risk of developing a secondary malignancy was most elevated for patients with an NEN of the lung, the stomach, and the ileum (60, 50 and 20 %, respectively). The spectrum of secondary malignancies included various types of cancer. Kaplan-Meier survival analysis shows a difference suggesting that patients with a secondary malignancy demonstrate a worse survival compared to patients without a secondary tumor; no significance was detected (p = 0.349). Our data suggest that secondary malignancies in patients with NEN's especially in GEP-NENs are found more frequently than in general population. Therefore, patients with NEN need a continuous and detailed follow-up. The reason for the increased incidence of secondary malignancies in patients with NENs remains to be elucidated.

Retrospective analysis of prognosticators in patients with relapsed Hodgkin’s Lymphoma treated with autologous transplant: results of a single center

Hodgkin's Lymphoma (HL) is highly chemoresponsive, and majority of patients respond to therapy except for a small number which require high-dose therapy and stem cell rescue for salvage. We report the results of a single-center experience in 41 patients with relapsed HL treated with high-dose therapy at the time of relapse from the year 1989-2010. The 7-year OS for the group is 39.2 %; the median progression-free survival is 30.6 months. Univariate analysis identified refractory disease at transplant and extranodal involvement as important prognosticators. The 100-day mortality was 5 %. The most common cause for delayed mortality was disease progression. The incidence of secondary malignancy in the group was 2 %. Our results reinforce the significance of long-term follow up as late relapses are observed. Additionally, identifying biological prognosticators and implying them for treatment may improve the outcomes in poor-risk patients.

Second malignancies after autologous haematopoietic stem cell transplantation following modified BEAM conditioning regimen in patients with Hodgkin lymphoma – characteristics and risk factors analysis

Aim of the studyThe aim of the study was to determine the incidence of second malignancies among patients with Hodgkin lymphoma (HL) treated with autologous haematopoietic stem cell transplantation (ASCT) following a modified BEAM (BCNU, etoposide, cytarabine, melphalan, dexamethasone) regimen between 1992 and 2012 at our department. We also intended to define the risk factors for the occurrence of second neoplasm after ASCT.Material and methodsThe long-term outcomes after transplant were evaluated in 170 patients, median age 31 years (range 17–61), who received a median of two pre-transplant chemotherapy lines (range 1–5).ResultsMOPP (mechlorethamine, vincristine, procarbazine, prednisone) or MOPP-type regimens were given to 12% of patients prior to ASCT. The median follow-up of the survivors was 73 (12–242) months. The 7-year overall survival and progression-free survival were 75% and 64%, respectively. Second malignancies occurred in 7 of the 170 patients, including 5 haematological malignancies, and 2 solid tumors. They developed at a median of 8 years (range 0.4–13.5) from ASCT. The 10-year and 15-year cumulative incidence of developing a second malignancy were 7% and 13%, respectively. In multivariate analysis, age ≥ 40 years at transplant (HR = 8.8; p = 0.008) and pre-transplant MOPP-type chemotherapy (HR = 5.6; p = 0.030) were the only factors significant for developing a second malignancy.ConclusionsOur results indicate that age of patient and the type of pre-transplant chemotherapy contribute to the risk of the development of a second neoplasm after ASCT in patients with HL. We believe that better characterization of second malignancies and associated risk factors may be useful for clinicians who care for these patients.

Secondary Myelodysplasia-Associated Metaphase Cytogenetic Abnormalities in Newly Diagnosed Multiple Myeloma Treated On Total Therapies 2 & 3– Influence of Cumulative Dosing of Maintenance Drugs

AbstractAbstract 324▪▪This icon denotes a clinically relevant abstract Background:There has been recent evidence that lenalidomide, while used in the treatment of myelodysplastic syndromes (MDS), also has been associated with an enhanced risk of secondary malignancies including MDS. Here we are examining the impact of maintenance on the development of metaphase-based MDS-associated cytogenetic abnormalities (MDS-CA), and subsequent development of therapy related MDS (t-MDS) and acute leukemia (t-AL) in the two arms of Total Therapy 2 (TT2) and two successive Total Therapy 3 trials (TT3A, TT3B). Methods:The details of TT2/TT3A/TT3B trials and patient outcomes have been reported previously. TT2 (median follow-up 118 months) patients were then randomized to receive thalidomide maintenance (TT2+Thal) for 3 years versus no thalidomide (TT2-Thal). Maintenance in TT3A (median follow-up 78 moths) consisted of VTD in the first year and TD for years 2 and 3 in TT3A, while TT3B (median follow-up 48 months) employed VRD for all 3 years. The patient populations were as follows: TT2-Thal arm (n=283), TT2+Thal arm (n=270), TT3A (n=279) and TT3B (n=162). Bone marrow examination with conventional cytogenetics was performed at baseline, post-induction, post-transplant and then at least semi-annually from maintenance in all patients prospectively. Chi-square and Fisher's exact tests were used to compare baseline characteristics between protocols. Univariate and multivariate Cox proportional hazard regression were used to model associations between baseline covariates and onset of MDS-CA and t-MDS/t-AL. Kaplan and Meier method was used to model cumulative incidence of MDS-CA and t-MDS/t-AL. Results:Baseline characteristics were fairly comparable between the two arms of TT2 and the two TT3 studies, except a higher proportion of GEP70 high risk patients in TT3B. Cumulative incidence of MDS-CA was significantly higher in TT3B protocol from time of first transplant (Figure 1), with the most common cytogenetic abnormality being deletion of chromosome 20 (del20, 35%), followed by monosomy/deletion 7 (27%) and monosomy/deletion 5 (17%) across all protocols. Of the 71 patients with an MDS-CA, 29 were also diagnosed with clinical MDS or AML; for these 29 patients, the median time to this diagnosis from first transplant was 58 months. The cumulative incidence of MDS-CA was higher and achieved more statistical significance (Figure 2) in TT3B compared to TT3A when landmarked from the start of maintenance. In univariate analysis for all patients, TT3B emerged as a significant variable in the univariate Cox regression model for MDS-CA, and in both the univariate and multivariate models for del20. Univariate and multivariate modeling within TT3B patient population did not reveal significance with cumulative dosing of different maintenance drugs. Discussion:Three randomized phase III trials (IFM-2005-02, CALGB 101104 and MM-015) have demonstrated an increase incidence of second malignancies in patients receiving lenalidomide maintenance after having been exposed to alkylating agent melphalan. In our present study, we are reporting an increased incidence of MDS-CA in the TT3B trial that employed VRD maintenance when compared with predecessor TT3A and TT2 trials. The data suggests that the risk is associated with lenalidomide exposure rather than its cumulative dosing in patients with prior exposure to therapy with alkylating agents. [Display omitted] Pairwise log-rank comparisons:TT3B vs. TT3A:p-value = 0.0206TT3B vs. TT2-Thal:p-value = 0.0134TT3B vs. TT2+Thal:p-value = 0.0178TT3A vs. TT2-Thal:p-value = 0.1502TT3A vs. TT2+Thal:p-value = 0.3134TT2-Thal vs. TT2+Thal:p-value = 0.8863 [Display omitted] Disclosures:Sawyer:University of Arkansas for Medical Sciences: Employment, under panding process, under panding process Patents & Royalties.

Secondary cancers after intensity‐modulated radiotherapy, brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause‐specific survival outcomes according to the initial treatment intervention

Study Type--Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis. • To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP). • Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n = 1348), EBRT (n = 897) or BT (n = 413). • Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs. • The 10-year SM-free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P = 0.002; RP vs BT, P = 0.37). • The 10-year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P = 0.29). • Multivariate analysis of predictors for development of all SMs showed that older age (P = 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable. • Among 243 patients who developed a SM, the 5-year likelihood of SM-related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P = 0.052). • The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history. • The incidence of bladder and rectal cancers was low for both EBRT- and BT-treated patients. • Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

Incidence of second and secondary malignancies in patients with CLL: A single institution experience.

6568 Background: Patients with chronic lymphocytic leukemia (CLL) have a higher incidence of second malignancies than the general population with one study showing the risk at 2.2 times the general popualtion. The increased incidence is thought to be due to immunosupression which results in decreased cell surveillance and proliferation of malignant cells. Our study aims to present the rate of second malignancies by cancer type in patients with CLL at our institution. Methods: The Moffitt Cancer Center Total Cancer Care (TCC) database was used to identify patients who had a diagnosis of CLL between January 1993-December 2009. Individual charts were reviewed to confirm the diagnosis of CLL, collect demographic data, and to assess for the presence of a second malignancy under an IRB approved protocol. A second malignancy was defined as another malignancy or transformation of CLL reported in the medical record. Second malignancy data was placed in three categories; skin cancers, solid tumor malignancy, and hematologic malignancy. Results: 546 CLL patients were included in the study. Median age was 62.5 years. 84 (43%) were Stage 0 and 62 (32%) were Stage 1 RAI at diagnosis indicating earlier disease. 266 (49%) patients had a second or secondary malignancy. A total of 304 cancers were identified. 14% of patients had more than one malignancy. Melanoma was identified in 44 (16.5%) patients and non-melanoma skin cancer was identified in 54 (20%). Lung cancer was identified as the most frequent solid tumor malignancy with 36 (13.5%) cases, followed by prostate (35), breast (21), colorectal (15), and bladder (14). 10 patients had a Richter’s transformation of their CLL. 26 patients developed either myelodysplastic syndrome or acute myelogenous leukemia. Conclusions: Second malignancies are frequent in CLL patients. Immunosupression, increased UV light exposure, longer life expectancy in low risk CLL, and tertiary cancer center referral bias are likely reasons for these increased rates. Further research is needed to identify the precise mechanism which cause patients with CLL to have higher rates of second malignancies and to identify if there is an increased risk of a specific type of malignancy in patients with CLL.