Occurrence Of Second Primary Malignancies Research Articles

The Risk of Second Primary Malignancies in Patients With Lung Neuroendocrine Tumors: A Population-Based Study on SEER Database

PurposeWe investigated the at-risk sites of second primary malignancies (SPMs) and evaluate the risk factors of SPMs among lung neuroendocrine tumors (LNETs) survivors by using the surveillance, epidemiology, and end results (SEER) database. MethodsPropensity-score matching was performed to conduct a case-control study from the surveillance, epidemiology, and end results (SEER) database. Cox regression analysis and multiple primary standardized incidence ratios were performed to investigate the risk factors of occurrence of SPMs among patients with LNETs. ResultsOf 3,206 patients with LNETs after matching, 539 developed SPMs. The risk of developing SPMs was higher in older patients (55–74 vs ≦54: hazard ratios [HR] 1.875; age ≧75 vs ≦54: HR 2.713), higher-stage of LNETs (regional vs localized: HR 1.387; distant vs localized: HR 2.732) and recent periods of diagnosis (2004–2014 vs 1984–1993: HR 1.735). Patients with SCLC, TC and LENEC had a higher risk for SPMs compared to general population. Lung and bronchus, larynx and some digestive organs had higher risk for SPMs while some sex hormone related organs like prostate, breast, and female reproductive system had a lower incidence of SPMs. ConclusionsPatients with LNETs had overall higher risks of SPMs than general population. Different types of second primary malignancies occurred in different periods after LNETs were diagnosed. Further investigations are required to screen different second primary malignancies for those with primary LNETs.

Increasing Incidence of B-Cell Non-Hodgkin Lymphoma and Occurrence of Second Primary Malignancies in South Korea: 10-Year Follow-up Using the Korean National Health Information Database.

PurposeThe epidemiology of B-cell non-Hodgkin lymphoma (BNHL) in Asia is not well described, and rates of second primary malignancies (SPM) in these patients are not known. We aimed to describe temporal changes in BNHL epidemiology and SPM incidence in Korea.Materials and MethodsA retrospective cohort study used claims data from the National Health Insurance Service that provides universal healthcare coverage in Korea. Newly diagnosed patients aged at least 19 years with a confirmed diagnosis of one of six BNHL subtypes (diffuse large cell B-cell lymphoma [DLBCL], small lymphocytic and chronic lymphocytic [CLL/SLL], follicular lymphoma [FL], mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], and lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia [WM]) during the period 2006-2015 were enrolled and followed up until death, dis-enrolment, or study end, whichever occurred first. Patients with pre-existing primary cancers prior to the diagnosis of BNHL were excluded. ResultsA total of 19,500 patients with newly diagnosed BNHL were identified out of 27,866 with non-Hodgkin lymphoma (NHL). DLBCL was the most frequently diagnosed subtype (41.9%-48.4% of NHL patients annually, 2011-2015). Standardized incidence of the six subtypes studied per 100,000 population increased from 5.74 in 2011 to 6.96 in 2015, with most increases in DLBCL, FL, and MZL. The incidence (95% confidence interval) of SPM per 100 person-years was 2.74 (2.26-3.29) for CLL/SLL, 2.43 (1.57-3.58) for MCL, 2.41 (2.10-2.76) for MZL, 2.23 (2.07-2.40) for DLBCL, 1.97 (1.61-2.38) for FL, and 1.41 (0.69-2.59) for WM. ConclusionBNHL has been increasingly diagnosed in Korea. High rates of SPM highlight the need for continued close monitoring to ensure early diagnosis and treatment.

Second primary malignancies among cancer patients.

BackgroundRate of second primary malignancies (SPM) is steadily increasing over the last decades. New therapies, early diagnostic markers, screening tests for a larger number of individuals contribute to the increase prevalence of SPM. In the current study, we try to described the demographic composition of SPM victims, distribution of primary sites, and the impact of related factors on prognosis.MethodsWe conducted a retrospective study identifying patients over the age of 18 who were diagnosed with SPM from the 16 most common cancer sites between 2000 and 2013 from Surveillance, Epidemiology, and End Results data. Cox proportional hazards regression was used to analyze the relationship between different factors associated to the prognosis of SPM. Standard incidence rate of multiple primary (MP-SIR) was also calculated.ResultsA total of 303,753 patients were diagnosis with SPM and 76,168 of whom (25.08%) were included in our analytic cohort. Patients with prostate cancer was vulnerable to SPM, accounting for 34.59%, and SPM was prone to occur in lung and bronchus, accounting for 24.90%. The heat map shows that esophagus cancer survivors have the highest risk of developing stomachache tumors (SIR =5.08). The result of Cox regression suggests that a history of liver was associated with the shortest survival time (HR =1.64, 95% CI, 1.54–1.75, P<0.001).ConclusionsWith the advancement of medical standards, the survival time of cancer patients is prolonged, but the occurrence of SPM is also increasing, and the prognosis is not optimistic. More attention needs to be invested in the prevention and treatment of SPM.

Occurrence of second primary malignancy in medullary thyroid cancer (MTC) patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Risk of Second Primary Malignancy in Multiple Myeloma in the Novel Therapy Era from 15 Years of Cancer Registry

Background: Novel agents such as thalidomide and bortezomib have changed the treatment landscape of multiple myeloma (MM). As patients with MM live longer, the risk of developing a second primary malignancy (SPM) increases. Few data describe the rate of SPM in patients with MM in Asia. Objectives: To describe SPM in patients with MM using the Taiwan Cancer Registry according to first-line treatment regimen. Methods: Connections between MM treatment and SPM were made by linking data from the Cancer Registry with the National Health Insurance Research database. All patients with a new diagnosis of MM (ICD-O-3 codes M-97323 and C42) in the cancer registry from 01 January 2000 until 31 June 2014 were included. Patients with a prior malignancy were excluded. Patients must have received at least one treatment for MM in the follow-up period with either novel agents alone, chemotherapy + novel agents, or chemotherapy alone. Patients were followed up for the occurrence of SPMs in the cancer registry from the diagnosis date until death, occurrence of the first SPM, or 31 December 2014, whichever occurred first. The incidence of SPM was calculated from the date of the first administered MM treatment. A competing risk model assessed possible effects of death on incidence rates. Results: There were 4327 eligible patients included in the cohort analysis. The mean age at diagnosis was 66.3 years (SD 11.8) and 57.8% were men. A total of 23.7% of patients received treatment with novel agents alone, 21.9% with chemotherapy + novel agents, and 54.4% with chemotherapy alone. Patients treated with novel agents were younger (mean age 64.4 years vs. 69.6 for chemotherapy + novel agents and 65.9 years for chemotherapy alone; p&lt;0.01) and had a higher incidence of renal impairment (18.1% vs. 15.6% and 11.6%, respectively; p&lt;0.01), whereas the co-morbidity index was lower in patients treated with chemotherapy alone (1.19, vs. 1.29 for novel agents and 1.28 for chemotherapy + novel agents; p=0.02). There were 91 (2.1%) patients who developed at least 1 SPM, of which 83.5% developed solid tumors and 16.5% developed a hematological cancer. The crude incidence of SPM per 1000 person-years from the date of first line treatment was 13.93 in patients who received chemotherapy + novel agents, 9.14 in patients receiving chemotherapy alone and 4.48 in patients who received novel agents alone (Table). In the competing risk model, the sub-distribution hazard ratio (adjusted for comorbidity index, sex, age and year of diagnosis) for developing at least one SPM was 3.34 (95% CI 1.51-7.39; p≤0.03) in patients treated with chemotherapy + novel agents, and 2.93 (95% CI 1.12-7.67 p≤0.03) in patients treated with chemotherapy alone as first line therapy in comparison with patients treated with novel agents alone. The 3-year cumulative probability was 1.88% for developing a solid SPM, and 0.47% for a hematological malignancy. The 3-year cumulative probability of developing any SPM was 0.71% in patients treated with novel agents, 4.88% after chemotherapy + novel agents, and 1.99% after chemotherapy alone (Figure). Conclusion: The availability of novel agents appears to be favorable for the prognosis of MM in terms of SPM development. This study shows that linking high quality databases increases the breadth and depth of knowledge that can be gained from real-world data and could be used in other disease areas. Disclosures Hou: Abbvie, Astellas, BMS, Celgene, Chugai, Daiichi Sankyo, IQVIA, Johnson &amp; Johnson, Kirin, Merck Sharp &amp; Dohme, Novartis, Pfizer, PharmaEssential, Roche, Takeda: Honoraria; Celgene: Research Funding. Liu:Janssen Research &amp; Development: Employment, Equity Ownership. Qiu:Janssen Research &amp; Development: Employment, Equity Ownership. Tien:Celgene: Research Funding; Alexion: Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Honoraria; Johnson &amp;Johnson: Honoraria; Daiichi Sankyo: Honoraria; Roche: Honoraria; Abbvie: Honoraria; Roche: Research Funding; Pfizer: Honoraria. Tang:GSK: Consultancy; Roche: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Amgen: Research Funding.

Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis

Background: Previously, studies have shown increased risks of second primary malignancies (SPM) after Hodgkin lymphoma and non-Hodgkin lymphoma. Nevertheless, investigation quantifying risks of SPM in patients with diffuse large B-cell lymphoma (DLBCL) remains scarce.Methods: We used the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub to analyze the risks of SPM in patients with DLBCL. The standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence intervals (CIs) were calculated.Results: Among patients with DLBCL as a primary malignancy, 3751 patients had second cancer episodes identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P < 0.05). There was a significantly higher risk of tumors/malignancies in the following sites of patients with DLBCL compared with the general population: Oral cavity and pharynx, hepatobiliary system, head and neck, thorax, bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently in patients with DLBCL than in the general population. Risk for a subsequent colon/rectum/anus cancer, bone and joint malignancy, and melanoma were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies was not significantly increased in those without a radiation record. Notably, for patients under 45 years of age, the risk for SPM was higher than their counterparts in other age groups.Conclusion: Our results offer insight into the occurrence of SPM among patients with DLBCL, suggesting awareness of the increased risk of subsequent malignancies is crucial for DLBCL survivors as well as for their physicians.

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial

BackgroundThe ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methodsIn a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. ResultsA total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660–1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468–0.879; P = 0.0051), and by IRC (0.735; 0.525–1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. ConclusionsATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration numberNCT01599754

An Increasing Trend of Incidence, Prevalence and Mortality, and Occurrence of Second Primary Malignancies Among Patients with B-Cell Non-Hodgkin Lymphoma: A 10-Year Longitudinal Population-Based Retrospective Cohort Study in South Korea

Background: Information about the epidemiology, treatment and clinical outcome of patients with B-cell Non-Hodgkin Lymphoma (BNHL) are limited and fragmented across Asia. Disparities in economy, health-care infrastructure, and access/reimbursement to novel drugs mean that treatment options and outcomes vary across the region. There is a need for improved understanding of real world treatment practices and outcomes in BNHL in Asian countries.Purpose: To describe incidence, clinical and treatment patterns and survival of patients with BNHL in South Korea.Methods: We conducted a retrospective cohort study using claims data from the National Health Insurance Service that covers 98% of all residents in South Korea. Newly diagnosed patients aged ≥18 years with a confirmed diagnosis of BNHL during the period 01 January 2006 to 31 December 2015 were enrolled. All eligible patients were followed up until death, dis-enrolment or the end of the observational period (December 31, 2015), whichever occurred first. Patients with pre-existing primary cancers were excluded. Standardized annual incidence, prevalence and morality rates were estimated. Overall survival and occurrence of second primary malignancies were estimated using Kaplan-Meier methods.Results: A total of 19,500 patients with newly diagnosed BNHL were included in the cohort analysis. At diagnosis, the mean age of patients was 59.5 years, 60.0% were 19-64 years of age and 54.0% were male. Diffuse large cell B-cell lymphoma (DLCBCL) was the most common diagnosis in each study year (53.1% to 58.7% of patients annually). The most commonly used first-line treatment regimens included rituximab-based combinations for the majority of patients with DLCBL, Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), or Chronic lymphocytic leukemia/ Small Lymphocytic Lymphoma (CLL/SLL), radiation for patients with Marginal Zone Lymphoma (MZL), and chlorambucil or cyclophosphamide for patients with Waldenström's Macroglobulinemia (WM).The overall incidence of BNHL increased over time, from 5.96 per 100,000 in 2011 to 6.99 per 100,000 population in (Table). BNHL prevalence increased steadily each year, and was 2.5-fold higher in 2015 than in 2011. The mortality rate increased by 50% over the same period, from 1.38 per 100,000 to 2.09 per 100,000 population. There was a trend of increasing incidence of some BNHL sub-types, mainly DLBCL, Follicular Lymphoma (FL), and Marginal Zone Lymphoma (MZL), over time (Fig. 1).There were 4009 patients between 2006-2015 (20.6%) who were diagnosed with at least one second primary malignancy more than 180 days after their BNHL diagnosis. The majority (96%) had a solid tumor; incidence rate of 5.93 per 100 person-years versus 0.24 per 100 person-years for hematological malignancies. By year 5, the cumulative hazard for developing a second primary malignancy was highest for CLL/SLL (25%) and lowest (18%) for FL. By year 8-9, the cumulative risk of developing a second primary malignancy was similar among the BHNL sub-types (Fig. 2).Five-year survival was 88% (95% Confidence interval [CI] 86-90) for MZL, 79% (95% CI 76-81) for FL, 62% (95% CI 59-66) for CLL/SLL, 60% (95% CI 59-61) for DLBCL, 54% (95% CI 47-63) for WM and 53% (95% CI 46-60) for MCL. Overall survival by year 9 was highest in patients with CLL/SLL and FL, lowest for WM (Fig. 3).Conclusion: The incidence, prevalence and mortality of BNHL appears to be increasing in Korea, and the occurrence of second primary malignancies is high. BNHL remains an important unmet medical need in South Korea. [Display omitted] DisclosuresLiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Qiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Rothwell:Janssen Research & Development, LLC: Employment, Equity Ownership.

European Post-Approval Safety Study (PASS) of Relapsed/Refractory Multiple Myeloma (RRMM): Safety, Including SPM, in a Large Cohort of Patients Treated with Lenalidomide, Thalidomide, and Bortezomib

Background: EU PASS is an observational, noninterventional study designed to investigate the safety of lenalidomide (LEN) and other agents in the treatment of RRMM in a real-world setting.Aims:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN), and second primary malignancies (SPMs) in RRMM patients (pts) treated with LEN and other antimyeloma therapies according to current clinical practice.Methods: Pts with RRMM who were commencing LEN treatment were enrolled at the investigator’s discretion into a LEN cohort (LEN + dexamethasone, the approved combination for the treatment of RRMM); pts who received ≥ 1 prior therapy and were commencing a non-LEN-based therapy were enrolled into a background cohort (all other treatments, including novel agents). Thromboprophylaxis was per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3). SPMs were defined using Medical Dictionary for Regulatory Activities (MedDRA) terms under the category Neoplasms SOC. Following protocol amendment in 2011, assessments for SPMs were to be conducted up to 36 mos after treatment discontinuation.Results: As of June 2016, 3632 pts across 269 institutions in 17 European countries were included in the safety population. Of those, 59.2% received LEN (n = 2151), 32.7% received bortezomib (BORT; n = 1188), 3.8% received thalidomide (THAL; n = 137), and 4.3% received other therapies (n = 156). The majority of pts had discontinued from treatment (97.9%; n = 3556); of the 2.1% (n = 76) ongoing pts, 66 are treated with LEN, 6 with BORT, 0 with THAL, and 4 with other substances. Baseline characteristics were similar across the cohorts. Median age was 70 yrs (range, 25-95 yrs) and 54.0% were male. Of 2985 pts with available ECOG data, 2865 (96.0%) had good performance status (ECOG score 0-2), and the remaining 4.0% had an ECOG score of 3/4. The median number of prior therapies was 1 (range, 1-6) but was higher in the LEN cohort (2; range, 1-6) than in the BORT (1; range, 1-6) and THAL (1; range, 1-5) cohorts; the proportion of pts with only 1 prior treatment was also lower in the LEN cohort (44.3%), whereas BORT was 70.8% and THAL 56.2%. Overall, 50.7% of pts (n = 1842) had grade 3/4 AEs. Grade 3/4 neutropenia occurred in 17.1%, 3.5%, and 4.4% of pts in the LEN, BORT, and THAL cohorts, respectively, and grade 3/4 thrombocytopenia in 9.2%, 7.3%, and 3.6%. The incidence rate of SPM was 3.63 per 100 pt-yrs, with 3.18 per 100 pt-yrs in the LEN cohort, 5.23 per 100 pt-yrs in the BORT cohort, 2.73 per 100 pt-yrs in THAL, and 6.48 per 100 pt-yrs in others. AEs of interest of all grades are listed in Table 1. The median duration on study treatment was 6.6 mos (range, 0.1-81.6 mos) for LEN, 4.1 mos (range, 0-63.6 mos) for BORT, and 4.6 mos (range, 0.2-36.9 mos) for THAL. Treatment discontinuation rate due to AEs was similar in each cohort (22.1% in the LEN, 20.0% in the BORT, and 21.2% in the THAL cohorts). In the LEN cohort, dose reductions occurred in 38.1% of pts, with a median time to first dose reduction due to AEs of 12.4 weeks. Treatment-emergent adverse events leading to dose reductions were similar across cohorts, with 23.7% in the LEN cohort, 21.4% in the BORT cohort, and 17.5% in the THAL cohort.Conclusions: Results of this noninterventional study in RRMM show that AEs were similar across cohorts except for higher rates of neutropenia and lower rates of PN with LEN compared with THAL or BORT. Higher rates of neutropenia did not translate into increased febrile neutropenia. Infections, independent from neutrophil counts, occurred in all cohorts, but few pts developed serious infections such as pneumonia. VTEs as well as myocardial infarctions were low throughout all cohorts. The occurrence of SPMs was generally low and comparable between cohorts. LEN was generally well tolerated. [Display omitted] DisclosuresTholouli:Johnson and Johnson: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria; MSD: Speakers Bureau; Giles: Speakers Bureau. Hájek:Janssen: Honoraria; Takeda: Consultancy; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Dimopoulos:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Frost Andersen:Celgene: Research Funding. Waage:Amgen: Speakers Bureau; Celgene: Consultancy, Honoraria; Novartis, Amgen, Celgene: Membership on an entity’s Board of Directors or advisory committees. Crotty:BMS, Takeda, Novartis, Janssen, Roche: Honoraria. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Di Micco:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership.

Second primary cancer after index head and neck squamous cell carcinoma in Northern China

To evaluate the clinicopathologic features, prognostic factors, and management of patients in the NorthChinese population with head and neck squamous cell carcinoma (HNSCC) who developed a second primary malignancy (SPM). This was a retrospective study including 1818 eligible patients between June 1999 and April2011. A total of 188 HNSCC patients developed SPM. Multiple oral dysplastic lesions (MODLs) (P<.001) were among the risk factors for occurrence of SPM. However, MODLs were closely associated with many mild pathologic features, such as early T stage (P<.001), early N stage (P=.036), good pathologic differentiation (P<.001), and mild growth pattern (P<.001). Interestingly, multivariate survival analysis showed that SPM patients had a better prognosis if they had the characteristics of MODLs (P=.020). MODLs were a crucial risk factor leading to the occurrence of oral SPM after an index HNSCC in patients in Northern China. However, SPM patients with the characteristics of MODLs had a better prognosis.

An Elderly Patient With Prostate Cancer and Colon Cancer 10 Years After a Diagnosis of Medullary Thyroid Carcinoma

Medullary thyroid carcinomas (MTC) are rare tumors that account for approximately 5-10% of all thyroid malignancy in the West. The reported incidence of MTC is less than 5% in Korea. Its prognosis is relatively good with a 15-year survival rate of 64-84%. The incidence of thyroid cancer has been increasing rapidly worldwide and the overall survival of patients with thyroid cancer is excellent. The occurrence of second primary malignancy (SPM) among survivors of thyroid cancer is a concern, together with life expectancy. Recent studies reported a 6-45% increase in the risk of developing SPM after the diagnosis thyroid cancer. We reported a patient with prostate and colon cancer that were diagnosed 10 years after the diagnosis of medullary thyroid carcinoma.

Connect MM®—the Multiple Myeloma (MM) Disease Registry: Incidence of Second Primary Malignancies (SPM)

▪Background: Increased rates of SPM have been observed as newer cancer treatments have improved survival over the past 2 decades (Fraumeni et al. NCI, 2006). Higher incidence of specific types of hematologic SPM following MM, especially acute myeloid leukemia and myelodysplastic syndromes, have been reported relative to the general population (Dores et al. NCI, 2006; Mailankody et al. Blood, 2011; Ravazi et al. Blood, 2011; Landgren and Mailankody. Leukemia, 2014). A complex interplay between myeloma-, host-, environmental-, and treatment-related factors likely contributes to the increased incidence of SPM in MM. Connect MM is the first and largest prospective, observational, US-based, multicenter registry designed to characterize patients (pts), treatment patterns, and outcomes in newly diagnosed MM (NDMM) pts.Methods: Between September 2009 and November 2012,a total of 1493 NDMM pts were enrolled from 234 US sites within 2 mos of the first diagnosis of MM. Patient data were collected at baseline and each subsequent quarter using a standardized form. Invasive SPM included hematologic and solid tumor second cancers and non-invasive SPM were defined as non-melanoma skin cancers (NMSC). SPM incidence and incidence rate (IR; number of pts with SPM per 100 patient-yrs [PY]) were calculated for all pts and by exposure to specific treatments, including lenalidomide (LEN). PYs were calculated as the observation period from the start of treatment until the detection of the first reported SPM (per category), death, or end of follow-up (pt lost or data cutoff).Results: As of Dec 10, 2013, SPM data were available for 1493 NDMM pts. The median age was 67 yrs (range, 24-94 yrs), 82% of patients were white and 57% were male. Median follow-up was 29.0 mos (0-49 mos). The median OS of treated pts was 44.4 mos. Fifty pts did not receive treatment and had no SPM reported. A total of 74 of the 1443 treated pts (5.1%) reported SPM. Invasive SPM were observed in 51 pts (3.5%): 37 pts (2.6%) with solid tumors and 14 pts (1.0%) with hematologic SPM. Lung/bronchus and myelodysplastic syndromes were the most frequently reported solid tumor and hematologic SPM respectively. NMSC were reported for 26 pts (1.8%). 3 pts had both an invasive SPM and NMSC. The IRs for invasive, hematologic, and solid tumor SPM by LEN exposure are listed in Table 1. By multivariate analysis, the only significant risk factor for the occurrence of SPM was prior history of invasive malignancy. Demographics (including age, ethnicity, race, and gender), International Staging System stage, family history of myeloma or other cancers, history of smoldering MM or monoclonal gammopathy of unknown significance, or prior radiation therapy were not associated with the occurrence of SPM.Conclusions: This analysis shows that there was no increased risk of invasive SPM in this disease-specific registry of pts with NDMM. The risk of SPM for LEN exposed pts was not greater than that for pts not exposed to LEN. In addition, multivariate analysis indicated the only significant risk factor for SPM was prior history of invasive malignancy. As additional agents are approved for the treatment of MM and the length of pt survival increases, longer prospective observation with expanded enrollment on the registry will better characterize the occurrence of SPM in this pt population. Correlations with risk factors including age, pre-existing MDS, risk status, as well as type and duration of therapy will continue to be investigated.Table 1Incidence rates (per 100 PYa) by treatment exposureIR per 100 PY (95% CI)SPMLEN-Exposed(n = 977)Non–LEN Exposed(n = 466)Invasive0.85 (0.61-1.19)1.16 (0.72-1.86)Hematologic0.17 (0.08-0.36)0.47 (0.22-0.99)Solid tumor0.67 (0.46-0.98)0.68 (0.36-1.26)NMSC0.50 (0.32-0.77)0.41 (0.18-0.91)a PY of exposure is the sum of exposure of all pts. DisclosuresRifkin:Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Shah:Celgene Corp: Consultancy, Research Funding. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity’s Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity’s Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity’s Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity’s Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Lu:Celgene Corp: Employment. Kenvin:Celgene Corp: Employment. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Durie:Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity’s Board of Directors or advisory committees; DMC Millennium: Membership on an entity’s Board of Directors or advisory committees; IRC J&J: Membership on an entity’s Board of Directors or advisory committees.

Simultaneous nasopharyngeal carcinoma with laryngeal squamous cell carcinoma and review of literature

The occurrence of second primary carcinomas (SPC) in aerodigestive tract is well recognized in the literature especially the lung and esophagus. The tumors are described according to the chronological presentation as simultaneous, synchronous and metachronous. Occurrence of second primary malignancy can be missed in early examination if they are not actively looked for. We are reporting the first and extremely rare presentation of nasopharyngeal carcinoma (NPC) presented simultaneously with laryngeal carcinoma with literature review and stress on the importance of pan-endoscopy in the management.

Newly Diagnosed Multiple Myeloma (MM) Patients Treated With Lenalidomide Induction and Maintenance Show a Low Incidence Of Second Primary Malignancies (SPMs)

Newly Diagnosed Multiple Myeloma (MM) Patients Treated With Lenalidomide Induction and Maintenance Show a Low Incidence Of Second Primary Malignancies (SPMs)

Pattern of second primary malignancies in thyroid cancer patients

Many factors, including relatively young age of thyroid cancer diagnoses and improved survival, have led to increased concerns about the occurrence of second primary malignancies. This paper describes the pattern of occurrence of second primary malignancies in patients who were treated for malignant thyroid neoplasms in an Indian hospital. There were 21 affected patients of the approximately 4500 seen over 25 years. Most of the second primary cancers are solid tumors, and when nonthyroid cancers are the second tumors, ductal carcinoma of the female breast is the most common. Most of these tumors have very short detection intervals (including synchronous occurrences), suggesting that therapy with internal radiation was not contributory to the tumor development. When thyroid malignancies were the second primary cancers, they usually follow radiotherapy to the head and neck region for treatment of the first primary tumor and tend to be of aggressive histologic types than the common well differentiated thyroid carcinomas.

Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas

An increased association between neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NET) and other second primary malignancies has been suggested. We determined whether there is indeed an increased risk for second primary malignancies in GEP-NET patients compared with an age- and sex-matched control group of patients with identical malignancies. The series comprised 243 men and 216 women, diagnosed with a GEP-NET between 2000 and 2009 in a tertiary referral center. The timeline, before-at-after diagnosis, and the type of other malignancies were studied using person-year methodology. Poisson distributions were used for testing statistical significance. All data were cross-checked with the Dutch National Cancer Registry. Out of 459 patients with GEP-NET, 67 (13.7%) had a second primary cancer diagnosis: 25 previous cancers (5.4%), 13 synchronous cancers (2.8%), and 29 metachronous cancers (6.3%). The most common types of second primary cancer were breast cancer (n=10), colorectal cancer (n=8), melanoma (n=6), and prostate cancer (n=5). The number of patients with a cancer history was lower than expected, although not significant (n=25 vs n=34.5). The diagnosis of synchronous cancers, mainly colorectal tumors, was higher than expected (n=13 vs n=6.1, P<0.05). Metachronous tumors occurred as frequent as expected (n=29 vs n=25.2, NS). In conclusion, our results are in contrast to previous studies and demonstrate that only the occurrence of synchronous second primary malignancies, mainly colorectal cancers, is increased in GEP-NET patients compared with the general population.

Analysis of Second Primary Malignancies in Lenalidomide-Treated Patients with IPSS Low- or Int-1-Risk Myelodysplastic Syndromes

Abstract 1704 Background:Lenalidomide (LEN) is approved in the US for the treatment of RBC transfusion-dependent patients with IPSS Low- or Int-1-risk myelodysplastic syndromes (MDS) with del(5q), with or without other cytogenetic abnormalities. In a phase 3 trial, treatment with LEN 5 mg and 10 mg resulted in RBC transfusion independence (TI) for ≥ 26 weeks in 43% and 56% of such patients, cytogenetic response in 25% and 50%, and a significant improvement of health-related quality of life (p <.05 for both 5 mg and 10 mg). Achievement of RBC-TI ≥ 8 weeks was associated with a significantly reduced risk of AML progression and death (p <.05 for both) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). In newly diagnosed multiple myeloma patients, results of phase 3 trials showed a numerical imbalance in the occurrence of second primary malignancies (SPMs) between patients treated with LEN (in combination with melphalan or immediately after high-dose melphalan therapy and stem cell transplantation) and control cohorts. SPMs were analyzed in clinical trials of LEN across indications, including MDS. Methods: This was a single arm analysis of SPM data retrieved from RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS with or without del(5q) who received LEN as monotherapy in 5 studies (MDS-001, -002, -003, -004, and -007). The cutoff date was February 28, 2011. SPMs were defined using MedDRA (Medical Dictionary for Regulatory Activities) categories of invasive SPMs (hematologic malignancies and solid tumors) and non-melanoma skin cancers (NMSC). Acute myeloid leukemia (AML) is considered part of the natural history of disease progression in MDS. Although further follow-up is needed, results of a phase 3 study showed no obvious evidence for an increased risk of AML progression in LEN-treated RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS and del(5q) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). AML was not included in the present analysis. The overall number of SPMs (invasive malignancies and NMSC), and the number and incidence rate (IR) of all invasive SPMs were evaluated, with IR defined as the number of new events per 100 person-years (pys). The IR of invasive SPMs was compared with the IR of new events of invasive cancer as reported from the SEER (Surveillance, Epidemiology, and End Results) cancer registry (2.1/100 pys for persons aged ≥ 65 years) (Howalder N et al. National Cancer Institute, 2011). Results: The combined population of all 5 studies comprised 557 LEN-treated patients. The median age was 71 years (range 27–95 years) and 72% of patients were aged ≥ 65 years. 88 patients (15.8%) had a prior history of cancer including malignant melanoma, meningioma, breast cancer, lung cancer, squamous cell carcinoma, and basal cell carcinoma. A total of 28 patients (5.0%) developed ≥ 1 SPM, including 17 (3.1%) with an invasive SPM and 12 (2.2%) with NMSC; 1 patient had both an invasive malignancy and a NMSC. Two of the 17 patients with invasive SPMs had a B-cell malignancy and 15 had solid tumors of heterogeneous type. Of the 28 patients with SPMs in total, 5 patients had a prior history of cancer. The IR of invasive SPMs was 2.60/100 pys (95% confidence interval 1.56–4.07), which is consistent with the IR reported in the SEER database among patients in this age group (2.1/100 pys for persons aged ≥ 65 years). The median time to onset of SPMs was 13.5 months (range 0.3–48.6 months). Conclusion: There was no clear evidence to associate LEN treatment with an increased risk of developing SPMs in patients with Low- or Int-1-risk MDS with or without del(5q). The IR of invasive SPMs among these LEN-treated patients is what would be expected from population-based estimates of invasive cancer incidence among persons in this age group. The collection of data on SPMs in LEN-treated patients including post-marketing information is ongoing. Disclosures:Giagounidis:Celgene Corporation: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. List:Celgene Corporation: Consultancy, Honoraria, Research Funding. Fenaux:Merck: Honoraria; Johnson & Johnson: Honoraria; Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Cephalon: Honoraria; Novartis: Honoraria. Benettaib:Celgene Corporation: Employment, Equity Ownership. Brown:Celgene Corporation: Employment, Equity Ownership. Zhong:Celgene Corporation: Employment, Equity Ownership. Brandenburg:Celgene Corporation: Employment, Equity Ownership. Mufti:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Occurrence of second primary malignancies in patients with nonmelanoma skin cancer in Asians

Occurrence of second primary malignancies in patients with nonmelanoma skin cancer in Asians

Impact of second primary malignancy on outcomes of differentiated thyroid carcinoma

There are few data on the degree to which thyroid cancer survivors are at risk of second primary malignancy (SPM). This study aimed at evaluating the risk of SPM in patients with differentiated thyroid carcinoma (DTC) and how the timing of SPM might affect the disease course. Among 1,043 patients diagnosed with DTC between 1970 and 2008, 27 (2.6%) had synchronous SPM (ie, diagnosed within 6 months of DTC) and 71 (6.8%) had metachronous SPM (ie, diagnosed > 6 months after DTC) in 10,419 person-years of follow-up. Standardized incidence ratios were estimated overall and for each SPM site. DTC survivors had a 39% greater risk of SPM (SIR = 1.39; 95% CI, 1.09-1.73) compared to the general population. Those with SPM had a worse overall survival than those without SPM (P < .001). The synchronous group had a worse DTC-specific survival (P = .002), whereas the metachronous group had a worse SPM-specific survival (P = .042). A lesser proportion in the metachronous group were able to receive curative treatment for SPM (32/71 vs 20/27; P = .013). DTC survivors had an increased risk of SPM. The occurrence of SPM adversely affected the survival of DTC. The synchronous group tended to die from DTC, whereas the metachronous group from SPM. Heightened postoperative surveillance might improve survival.

Salivary Gland Malignancy and Radioiodine Therapy for Thyroid Cancer

The risk of second primary malignancies in patients with well-differentiated thyroid cancer is of special interest because of the common use of radioactive iodine (RAI) ablation and/or treatment of these patients and the theoretical risk of subsequent nonthyroid malignancies associated with the radiation exposure. This brief report focuses specifically on the occurrence of second primary malignancies of the salivary glands. RAI residency within salivary tissues is known to have both acute and chronic consequences on salivary function, but secondary neoplasia is quite unusual. We present a very rare case of a patient with papillary thyroid cancer treated with 600 mCi of RAI, who subsequently developed salivary gland cancer. We recommend salivary gland protection to diminish potential side effects after the exposure to radioiodine. On the basis of our experience we suggest administration of sialogogues (such as lemon juice) continuously, every 30-60 minutes for 24 hours, after RAI administration.