Second Malignancies In Patients Research Articles

Occurrence of Secondary Non-Hodgkin Lymphomas Among Our Classical Hodgkin Lymphoma Patients: A Single-Centre Experience.

Objective Non-Hodgkin lymphoma (NHL) arising as a secondary malignancy in patients treated for classical Hodgkin lymphoma (cHL) is an infrequent and challenging clinical scenario. NHL can be presented synchronously with cHL or may develop later, sequentially, up to years after treatment for cHL. The relationship between the two lymphomas is unclear, and there are no clear guidelines forthe management ofthese patients. We would like to find a better clinical understanding of this issueso this study investigates the occurrence and clinical characteristics of secondary NHL. Materials and methods In this retrospective cohort examination, we collected cHL cases when NHL occurred during or after the course of treating cHL. We performed the histopathologic revisions of the samples, and in every case where the quality of the sample was lower, we performed molecular examinations to find the association between cHL and NHL. We performed next-generation genome sequencing (NGS) and immunoglobulin heavy-chain variable region gene (IgHV) clonality testing. Results In a cohort of 164 cHL patients diagnosed between 2011 and 2020, six patients were identified with NHL during rebiopsy prompted by lymphoma relapse or progression. Among these, five patients were diagnosed with post-germinalcenter-originated diffuse large B-cell lymphoma (post-GC DLBCL), and one patient presented high-grade B-cell lymphoma (HG-BCL). The NHL manifestation differed in its timing: three cases emerged after successful cHL treatment, with at least 18 months of complete remission, while the other three patients faced primary refractory cHL. Notably, the primary refractory cases did not exhibit a confirmed clonal relationship between cHL and NHL, but NGS data raised the possibility of synchronous NHL in one case. In contrast, among the patients with sequentially occurring NHL, polymerase chain reaction (PCR) testing of the IgHV gene affirmed a clonal connection between cHL and secondary DLBCL in one case, while the high morphological similarity suggested a potential clonality between the two lymphomas in another case. Conclusion This study reveals that secondary NHL may manifest both synchronously and sequentially following cHL. Our results suggest that synchronous NHL has a worse prognosis compared to sequentialcaseswhen the different lymphomas are not recognized at the time of diagnosis. As our data showed, in some cases, mutations that accompany the tumor cells throughout their clonal evolution can be identified, with additional mutations later on. In the future, next-generation sequencing (NGS)-based processing of liquid biopsy samples can overcome the limitations resulting from the spatial heterogeneity of lymphoid malignancies. Over the long term, this identification could lead to early patient selection and alternative treatment strategies, ultimately leading to improved prospects for cure.

Long-Term Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy.

Second malignancy is a rare but potentially lethal event after prostate brachytherapy, but data remain scarce on its long-term risk. The objective of this study is to estimate the number of pelvic second malignancies following brachytherapy compared to radical prostatectomy (RP). We retrospectively reviewed patients treated with low-dose 125I brachytherapy and RP in British Columbia from 1999 to 2010. Kaplan-Meier estimates for pelvic (bladder and rectum), invasive pelvic, any second malignancy, and death from any second malignancy were assessed. Cox multivariable analyses were performed adjusting for initial treatment type, age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking history. Two thousand three hundred seventy-eight brachytherapy and 9089 RP patients were included. Median age was 66 years (interquartile range [IQR] 61-71) and 63 years (IQR 58-67), respectively. Median follow-up time to event or censured was 14 years (IQR 11.5-17.3). The Kaplan-Meier estimates for pelvic second malignancy at 15 and 20 years were 6.4% and 9.8%, respectively, after brachytherapy, and 3.2% and 4.2% after RP. Time to any second malignancy and time to death from any second malignancy were not significantly different (P > .05). On Cox multivariable analysis, brachytherapy, compared to surgery, was an independent factor for pelvic (hazard ratio [HR] 1.81 [95% CI 1.45-2.26], P < .001) and invasive pelvic second malignancy (HR 2.13 [95% CI 1.61-2.83], P < .001). Increased age and smoking were also associated with higher estimates of events (P < .001). After adjustment for age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking status, numerically higher long-term HRs of pelvic and invasive pelvic second malignancy in patients treated with brachytherapy compared to RP were noted.

Risk of second cancers in long term survivors of neuroendocrine tumors of the large intestine.

600 Background: There is an increasing incidence of neuroendocrine tumors (NET) of the colon and rectum likely related to increased screening colonoscopy and availability of better diagnostics. Most of these tumors identified during screening are low grade early-stage tumors with high cure rates. Data on long term risk of recurrence of NET and other second cancers is lacking. We studied the incidence rates of all second malignancies in survivors of NET of the colon and rectum. Methods: We analyzed data from the Surveillance, Epidemiology and End Results (SEER), Research Data 17 Registries, Nov 2022 Sub (2000-2022) to determine the risk of second malignancies in patients with an initial cancer diagnosis of NET of the colon and rectum. With these criteria we had overall 17,907 patients and 157,720 patient years of follow up. The relative risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E]). Incidence ratios are analyzed over time from initial diagnosis to assess long term risk. Results: Survivors of NET of the large intestine are at highest risk of malignancy of the rectum (O/E: 6.4, CI: 7.26 - 5.21, N= 239) and this increased risk of rectal cancer persists even 10 years after the initial diagnosis (0/E: 3.8, CI: 5.37- 2.6, N= 32). There is no increased risk of cancer of the colon excluding rectum (O/E: 0.98, CI: 1.18-0.81, N= 114). Even after 10 years from diagnosis there is increased risk of recurrence of the NET of the Colon (O/E: 1.28, CI: 1.55-1.06, N=110) and NET of the Rectum (O/E: 1.12, CI: 1.23- 1.02, N= 433). There is also increased incidence of small intestine cancer (O/E: 2.92, CI: 4.17- 1.97, N=30), Prostate cancer (O/E: 1.28, CI: 1.41- 1.15, N=400), Kidney and renal pelvis cancer (O/E: 1.53, CI: 1.86 -1.25, N= 104), Thyroid cancer (O/E: 1.63, CI: 2.12-1.23, N= 55) and Nodal Non-Hodgkins Lymphoma (O/E: 1.34, CI: 1.71-1.03, N=64). Conclusions: Survivors of NET of the large intestine are at risk of developing subsequent malignancies. The information presented may help physicians in effectively monitoring survivors for second cancers at various timeframes from their initial diagnosis.

Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Incidence of second malignancies in patients with thymic carcinoma and thymic neuroendocrine tumor

ObjectivesThymic carcinoma and thymic neuroendocrine tumor (NET) are rare and are more likely to develop second malignancies. The purpose of this study was to explore the incidence and lifetime risk of second malignancies in thymic carcinoma and thymic NET.MethodsThe standardized incidence ratio (SIR) and the age-adjusted cancer incidence of the thymic carcinoma and thymic NET patients with second malignancies were retrospectively calculated by using the Surveillance, Epidemiology, and End Results (SEER) database. Prognosis results were also determined by Kaplan–Meier analysis and Cox regression.Results1130 patients with thymic carcinoma (73 patients had second malignancies) and 263 patients with thymic NET (19 patients had second malignancies) from 2000 to 2018 are included. Patients with thymic carcinoma (SIR: 1.36, 95% CI 1.08–1.69) and with thymic NET (SIR: 1.73, 95% CI 1.13–2.54) demonstrate an increased overall risk of developing second malignancies in various organ systems. The age-adjusted cancer incidence of second malignancies in patients with thymic carcinoma is 3058.48 per 100,000 persons (4178.46 per 100,000 persons in patients with thymic NET). Age at diagnosis is a significant risk factor for the development of second malignancies.ConclusionThe incidence of second malignancies in patients with thymic carcinoma and thymic NET is significantly higher than the patients in the normal population. The occurrence of second malignancies is not related to the use of different treatments. It is important to extend the follow-up period and add other screening methods.

Secondary Malignancies in Patients after Allogeneic Hematopoietic Cell Transplantation at Triple the Incidence of Malignancies in Their Family Donors

The primary end point of this retrospective study was to determine the incidence, risk factors and clinical outcome of secondary malignancies in 951 patients who were given an allogeneic Hemopoietic Cell Transplantation (HCT) and to compare them with the incidence of malignancy observed in the cohort of 761 stem cell family donors. With a median follow-up of 20 years, 74 HCT recipients (40 males) developed SM at a median of 16.09 years since transplant and at a median age of 47 years. The 35-yr cumulative incidence of SM was 17.0% (95% confidence interval, 12.8-21.6%). In univariate analysis, factors associated with increased incidence of SM were cumulative (limited and extensive) chronic graft-versus-host disease (cGvHD) and duration of cumulative cGvHD &gt;24 months. By multivariate analysis, cumulative cGvHD was the only independent risk factor for SM. Patients with cGvHD had 2.85x higher risk as compared to patients without cGvHD (P&lt;0.001). With a median follow-up of 18 years, 13 family donors (7 males) out of 761 developed malignancy at a median of 15.04 years since stem cell donation and at a median age of 55 years. As compared to the cumulative incidence of SM observed in the cohort of transplant recipients, the cumulative incidence of malignancy in family donors at 35 years since stem cell donation was statistically lower [5.8% vs 17.0% (P=0.001)]. This study demonstrates that HCT recipients have a significantly higher incidence of developing post-transplant malignancy as compared to family donors and that cGvHD is a strong risk factor for SM development.

Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances.

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL patients, the chance of developing secondary leukemia is manifold compared to that in the general pediatric population, and the prognosis for patients with secondary leukemia is much worse than that for patients with other hematological malignancies. Therefore, it is crucial to develop clinically useful biomarkers to stratify patients according to their risk of late malignancies and determine which require intense treatment regimens to maintain the ideal balance between maximizing survival rates and avoiding late consequences. In this article, we review HL's epidemiology, risk factors, staging, molecular and genetic biomarkers, and treatments for children and adults, as well as treatment-related adverse events and the late development of secondary malignancies in patients with the disease.

Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram.

Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram. A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established. Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, "bone and joint neoplasms" (SIR = 11.07, 95% CI, 5.52-19.81) and "soft tissue neoplasms" (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas "breast cancer" and "endocrine cancer" associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively. The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.

225MO Clinical, pathologic and immune-related features of radiation-associated oral cavity squamous cell carcinoma: A matched cohort study

Post-radiation (RT) oral squamous cell carcinoma (OCSCC) is a common second malignancy in patients with nasopharyngeal carcinoma, often with a lethal outcome. We conducted a retrospective comparative analysis on the clinicopathologic features of post-RT OCSCC with demographic-matched sporadic OCSCC to shed light on their distinctive clinical behaviors.

Second primary malignancies (SPM) in patients with gastrointestinal stromal tumors (GIST): 10-year experience from the Ottawa Hospital (TOH).

11536 Background: The secondary malignancies in patients with GIST are relatively high. We present our 10-year experience of SPM in patients with GIST from a regional Cancer Centre in Canada. Methods: A retrospective cohort study was performed in all GIST patients treated at TOH between January 2011 and December 2021. Patients were identified using ICD-10 codes and electronic medical records reviewed. Clinicopathological data were analyzed. Logistic regression analysis was used to evaluate associated factors with SPM. Survival analysis was estimated with the use of the Kaplan-Meir method and compared by log-rank test. Results: In total, 248 patients with GIST were identified. Of these patients, 61 (25%) had SPM; synchronous (9, 15%) and metachronous (52, 85%). Nine patients had two additional primary cancers other than GIST, and four patients had three additional primary cancers. The median age at diagnosis was 70 (range 44 – 90) years, and males were (59%). The most common SPMs were skin cancer (14, 17%), melanoma (5), and non-melanoma (9), followed by prostate cancer (13, 16%) and breast cancer (12, 15%). Colorectal cancer and hematological malignancies were found in (5, 11%) patients each, while RCC was found in (4, 6%). Thyroid cancer, lung cancer, neuroendocrine tumor, bladder cancer, thymoma, and other types of cancers were collectively found in 15 patients (24%). The majority (57%) of SPM diagnosed before GIST, 30% after GIST. The most common primary GIST locations were in the stomach (62%), followed by the small bowel (30%), and the most common histology was spindle cell (69%), followed by mixed histology (13%). The majority of GIST were localized (46 patients, 75%). Based on Miettinen risk classes for non-metastatic GIST, 74% had zero to low-risk disease, while 26% had moderate or high-risk disease. There was no association between SPM and GIST primary site (p = 0.4), TNM stage (p = 0.8), histology (p = 0.2), Mitosis (p = 0.5), and Miettinen risk class (p = 0.6). The median follow-up time was 53 months (range 1 – 132), and four patients lost follow-ups. Five years overall survival of SPM group vs. non SPM, 79.8% vs. 94.1%, (p = 0.03). Cox regression did not reveal a significant association with the covariants Conclusions: We observed that one out of four GIST patients have SPM. Skin, prostate, breast cancers were the most common SPM associated with GIST. Molecular studies are needed to explore the association/underlying mechanisms of GIST with these malignancies.

Clinical Implications of Pathogenic Germline Variants in Small Intestine Neuroendocrine Tumors (SI-NETs).

An inherited basis for presumed sporadic neuroendocrine tumor (NET) has been suggested by evidence of familial clustering of NET and a higher incidence of second malignancies in patients and families with NET. To further investigate a potential heritable basis for sporadic neuroendocrine tumors, we performed multigene platform germline analysis to determine the frequency of hereditary susceptibility gene variants in a cohort of patients with sporadic small intestine NET (SI-NET). We performed a multigene platform germline analysis with Invitae's 83-gene, next-generation sequencing panel using DNA from 88 individuals with SI-NET from a clinically annotated database of patients with NET evaluated at Dana-Farber Cancer Institute (DFCI) who are considered high risk for inherited variants. Additionally, we evaluated the prevalence of pathogenic variants in an unselected cohort of patients with SI-NET who underwent testing with Invitae. Of the 88 patients in the DFCI cohort, a pathogenic germline variant was identified in eight (9%) patients. In an independent cohort of 120 patients with SI-NET, a pathogenic germline variant was identified in 13 (11%) patients. Pathogenic variants were identified in more than one patient in the following genes: ATM, RAD51C, MUTYH, and BLM. Somatic testing of tumors from the DFCI cohort was suboptimal because of insufficient coverage of all targeted exons, and therefore, analysis was limited. We demonstrate a 9%-11% incidence of pathogenic germline variants in genes associated with inherited susceptibility for malignancy not previously described in association with SI-NET. The association of these germline variants with neuroendocrine carcinogenesis and risk is uncertain but warrants further characterization.

Prevalence of Secondary Malignancies in Patients with Mycosis Fungoides and Sézary Syndrome

Prevalence of Secondary Malignancies in Patients with Mycosis Fungoides and Sézary Syndrome

Epi-P-03 - Association between primary cutaneous lymphomas and other primary malignancies in patients’ personal or family history in Greek population; a retrospective single-center study

<h3>Background:</h3> Primary cutaneous lymphomas (PCLs) consist of an heterogenous group of rare malignancies. Cutaneous T-cell lymphomas are the most common among them, with mycosis fungoides being the main representative. The etiology of PCLs is rather unknown; however, there are indications that genetic factors may play a role in CTCL developments [1]. Several studies have examined the incidence of second malignancies in patients with PCLs, as well as their family history of malignancies [2–4]. In our study we examine the association between PCLs and other primary malignancies in patients' personal or family history in Greek population. <h3>Methods:</h3> This retrospective study included 144 patients with histopathologically confirmed diagnosis of PCL and 130 controls matched by gender and age (±4 years). All patients and controls completed a detailed questionnaire regarding sun exposure habits-including personal history of sunburns, use of photo-protective measures, use of sunbeds- exposure to ionizing radiation, smoking and alcohol consumption habits, detailed medical personal history (diseases, medication, other chronic skin conditions, personal history of malignancies, etc.) and family history (chronic skin conditions, malignancies). Statistical analysis of the data was performed using PASW Statistics v25 software. <h3>Results:</h3> Of the 144 patients included, 78 (54.2%) were males and 66 (45.8%) females (median age 57 years old) and among the 130 control subjects, 70 (53.8%) were males and 60 (46.2%) females (median age 61 years old). Analysis showed that family history of solid organ cancer is related to higher relative risk (OR 1.815) of CL development (p<0.05, 95% CI 1.11–2.95). The two types of solid organ tumors more highlighted were liver cancer (p=0.046) and stomach cancer (p=0.002). Family history of skin cancer as well as hematologic malignancies doesn't seem to affect the risk of CL in statistically significant way (p=0.247 and p=0.093 relatively) in our group. As far as the personal history of other primary malignancies is concerned, statistical analysis showed that there might be a correlation between other malignancies and primary cutaneous lymphomas (p<0.05). At this point we should notice the limitation that the number of patients and controls having a personal history of any type of cancer was small, but it consists a predictor. <h3>Conclusion:</h3> There are several studies analyzing the correlation of PCLs and second primary cancers. The results of our study showed an association of personal history of cancer with PCLs, as well as a correlation of family history of solid organ malignancy with a higher relative risk of cutaneous lymphoma development. No higher relative risk was detected in subjects with family history of hematologic malignancies. We believe that it is important to be aware of the personal and the family history of patients with PCL, as far as the malignancies are concerned, and try to early recognize possible second malignancies in these patients.

Possible Role Of Treatment On Secondary Malignancies In Patients Affected By Essential Thrombocytemia

IntroductionSurvival of Essential Thrombocytemia (ET) patients in the first 10 years of disease follow-up is similar to the general population one. While it is well known that alkylating agents (given alone or sequentially) increase the risk for acute myeloid leukemia, the specific role of different therapies on the development of secondary malignancies (SM) in ET patients, is still under investigation. AimsTo retrospectively evaluate the role of different treatments on the development of SM in a large population of ET patients. Patients and methodsWe collected a series of 1026 ET patients (diagnosis period 1980-2010), followed in 11 Hematological Centers (universities 5, general hospitals 6) from the region Lazio in Central Italy. Median age at ET diagnosis is 62.5 years (range 17-93); 392 males, 634 females; median follow-up of the entire population is 6.2 years (range 0.1 – 31.9). Seventy/1026 patients (6.8%) developed 71 SM during follow-up. Observed SM were grouped as follows: genito-urinary 15, breast 14, non-melanoma skin cancer 12, lung 11, gastro-intestinal 8, hematologic 5, thyroid 3, central nervous system 1, soft tissue 1 and unknown 1.Taking in consideration the different treatment approach, we divided our population in 5 different groups: group 0, no treated patients; group 1, patients treated either with Hydroxiurea (HU) alone or in combination/sequentially with Interpheron (IFN)/Anagrelide (ANA); group 2, patients treated either with alkylating agents (ALK) alone or in combination/sequentially with IFN/ANA; group 3, patients treated with ALK + HU sequentially; group 4, patients treated with ANA and/or IFN only. Characteristics of the patients are shown in the table. Results and conclusionsTaking into account every single treatment group, although we observed an increased rate in the ALK one (4/26, 15.4%), we could not find a statistically significant difference in the risk of SM development. Instead, combining different groups we obtained the subsequent results: group 0 + 4 versus group 1, no statistically significant difference (p= 0.174); group 0 + 4 versus 2 + 3 statistically significant difference (p= 0.031). Compared to anagrelide, interferon or no treatment, alkylating agents alone or given sequentially with hydroxiurea, seem to increase the risk of SM development, while HU treatment alone do not. Disclosures:No relevant conflicts of interest to declare.

Incidence of Secondary Malignancies in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Era of Tyrosine Kinase Inhibitors (TKI)

IntroductionWith TKI therapy the survival of patients with CML-CP is approaching to that of general population. Data on the incidence of secondary malignancies in CML is conflicting given the rarity of CML and the low incidence of secondary malignancies. The aim of this study is to evaluate the incidence of secondary malignancies in patients with CML-CP in a large US-based database.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database identified 13,276 patients with newly diagnosed CML-CP during the period from 2001 to 2014. Patients who had prior history of cancer, concurrent diagnosis of other malignancies at the same diagnostic year, and patients who developed secondary leukemia after the diagnosis of CML were excluded. Cumulative incidence of secondary malignancies were estimated with the presence of competing risk of death. Standard incidence ratio (SIR) was calculated from person-years at risk divided by expected cases based on the age-adjusted incidence ratio of the 2000 U.S. standard population.ResultsOf 13,276 patients, secondary malignancies were observed in 597 patients (4%) with a median follow-up of 69 months (Table 1). The three most common secondary malignancies were male genital system 130 (22%), digestive system 124 (21%) and respiratory system, 92 (15%). The 5-year and 10-year cumulative incidence of death for all patients was 30.5% (95% confidence interval [CI], 29.6-31.4), and 41.8% (95% CI, 40.7-43.0). The 5-year and 10-year cumulative incidence of secondary malignancies were 4.4% (95% CI, 4.0-4.8), and 7.2% (95% CI, 6.6-7.9), respectively (Figure 1). Overall SIR was 1.204 (95% CI, 1.108-1.301). The increased SIRs were observed in male genital system of 1.593 (95% CI, 1.319-1.866); digestive system, 1.291 (95% CI, 1.064-1.519); skin, 1.588 (95% CI, 1.083-2.093); urinary system, 1.366 (95% CI, 1.008-1.724); and miscellaneous, 1.877 (1.033-2.721) (Figure 2). The decreased SIR was observed in breast cancer of 0.665 (95% CI, 0.479-0.852). Overall excess absolute risk was 1.714 per 1,000 person years at risk (95% CI, 0.622-2.805).ConclusionRelative incidence of overall secondary malignancies in CML-CP is slightly higher than that of general population with minimal increase in the excess absolute risk. Given the limitation of registry data, the uncertainty of use and type of TKI, and response status at the diagnosis of secondary malignancies, conclusions regarding actual risk should be cautiously interpreted. It is also at this stage not possible to determine whether any possible increased risk is associated with the diagnosis of CML-CP per se or the use of TKIs. Further analysis is needed. [Display omitted] DisclosuresKantarjian:Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding. O'Brien:Amgen: Consultancy; Alexion: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Janssen: Consultancy; Vaniam Group LLC: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; GSK: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; Regeneron: Other: Research Support: Honorarium, Research Funding; Aptose Biosciences, Inc.: Consultancy; ProNAI: Other: Research Support: Honorarium, Research Funding; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy. Wierda:Emergent: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; The University of Texas MD Anderson Cancer Center: Employment; Acerta: Research Funding; Kite: Research Funding; GSK/Novartis: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Juno: Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding. Daver:Daiichi-Sankyo: Research Funding; Kiromic: Research Funding; Incyte Corporation: Honoraria, Research Funding; Jazz: Consultancy; Bristol-Myers Squibb Company: Consultancy, Research Funding; Otsuka America Pharmaceutical, Inc.: Consultancy; Karyopharm: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Immunogen: Research Funding; Pfizer Inc.: Consultancy, Research Funding; Sunesis Pharmaceuticals, Inc.: Consultancy, Research Funding. Takahashi:Symbio Pharmaceuticals: Consultancy. Jabbour:Bristol-Myers Squibb: Consultancy. Cortes:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Sun Pharma: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding; ImmunoGen: Consultancy, Research Funding; ARIAD: Consultancy, Research Funding.

Second Primary Malignancies in Long Term Acute Lymphoblastic Leukemia Survivors of Three Age Groups

Background:Survivors of Acute Lymphoblastic Leukemia (ALL) are at an increased risk of subsequent malignancies secondary to genetic makeup, and exposure to environmental and treatment factors. Younger patients are exposed to different risk factors than older patients, which may result in differences in the risk of second malignancies. Additionally, there is not much information regarding the long term risk of subsequent malignancies. Therefore, we conducted this study to analyze and compare the risks of all second malignancies in patients aged under 15 (pediatric), 15-39 (Adolescent and Young Adult) and over 40 (Adults), five years after their initial diagnosis.Methods:Using data from the Surveillance, Epidemiology and End Results 9 database, Nov 2016 Sub {1973-2012}, we determined the risk of secondary malignancies in long term (five years out from diagnosis) survivors of ALL belonging to three age groups at diagnosis: less than 15, 15 to 39, and 40 and above. For the first cohort, patients younger than 15, there were 5200 patients with 69651 patient years of follow up. For the second age cohort, 15-39, there was a total of 949 patients with 10703 patient years of follow up, and for the third cohort, patients aged 40 and over, there were 365 patients with 2497 patient years of follow up. The risk of second primary malignancies is given as the standardized incidence ratio, which is calculated as such: observed incidence[O]/expected incidence[E]Results:Five years after an ALL diagnosis, patients under the age of 15 are at the highest relative risk of developing any type of second cancer (O/E: 3.58; CI: 2.95-4.30; N=114). Patients between the ages of 15-39 had a significantly fewer number of total cases, but still presented a high relative risk of developing any second malignancy (O/E: 1.59; CI: 1.10-2.22; N=34). Although patients over 40 had more total cases of second cancers than patients between 15-39, the data did not present any statistical significant increased relative risk for developing a second cancer when compared to matched population (O/E: 1.06; CI: 0.76-1.44 ; N=41). Patients under the age of 15 are at the highest risk of developing a second cancer of the salivary gland (O/E: 39.75; CI: 17.16-78.33; N=8). For patients under the age of 15, cancers of the oral cavity and pharynx (O/E: 15.38; CI: 7.37-28.28; N=10), brain, (O/E: 10.98; CI: 6.79-16.78; N=21) and thyroid (O/E: 7.07; CI: 4.70-10.21; N=28) represent the highest number of second cancers. Similarly, patients aged 15 to 39 are also at a high risk of developing a cancer of the salivary gland (O/E: 25.70; CI: 3.11-92.85; N=2). For patients aged 40 and above, cancer of the gum and other mouth has the highest increased risk (O/E: 14.73; CI: 1.78-53.22; N=2), but again there are relatively few patients so we cannot make any accurate estimates for second cancers. This decrease in the total number of patients may be due to an increase in the number of deaths resulting from ALL. In the database analyzed patients over 40 surviving one year, we had a total of 1,287 patients, but the same age cohort 4 more years from initial diagnosis only had 365 patients. Only 28% of patients over 40 survived after 5 years.Conclusion:There are several second malignancies that long term survivors of ALL are at increased risk of developing, even after 5 years from their initial diagnosis. These risks vary by age group, with young patients at substantially higher relative risk compared to their peers. However, unfortunately most adult patients died within the first five years of diagnosis. This information may help physicians effectively monitor survivors of ALL of all ages for any second cancers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence and patterns of secondary malignancies in patients with neuroendocrine neoplasms: A SEER database analysis.

e16208 Background: Neuroendocrine neoplasms (NENs) are a group of biologically and clinically heterogenous malignancies of different anatomic sites, the majority of which lie within the gastrointestinal (GI) tract. Prior literature has reported on the association between NENs and other primary malignancies (OPM), but these studies are limited by small sample sizes. We aim to further analyze the association of NENs and OPM on a larger scale using a population-based cancer registry. Methods: Primary malignancies with NEN features were identified from the Surveillance Epidemiology and Ends Results registry between 1975-2017. The histology/behavior of NEN included carcinoid tumor, neuroendocrine carcinoma (NEC), pancreatic endocrine tumor, atypical carcinoid tumor, and other (insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid). First NEN observation from each patient was examined. Patients with NEN were grouped into 3 categories: NEN only, NEN first followed by OPM, and non-NEN first followed by NEN based on sequence number of primary cancer. Secondary malignancy sites were analyzed. Distribution of NEN between GI and non-GI sites was described. Demographics were compared by NEN sequence groups and between GI and non-GI sites. Results: 45,896 patients with NEN were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 yrs). 65.7% of NENs were observed in GI sites. Within the GI tract, 31.3% were small intestine, 25.1% rectum, 16.6% pancreatobiliary, and &lt; 11% in other GI locations. Age at NEN diagnosis was younger in those with GI NENs (median 60.0 vs 65.0, p &lt; 0.001). 71.2% of patients had NEN only, 10.4% had NEN first followed by OPM, and 18.4% had a non-NEN primary followed by NEN. Mean age was 58.9 for NEN primary only, 61.0 for NEN primary first and 68.3 for non-NEN primary first (p &lt; 0.0001). More Caucasian patients had non-NEN primary first (82.3%) compared to NEN primary only (76.9%) and NEN primary first (75.5%). There were no gender differences amongst the three groups. Carcinoid tumor histology was more prevalent in NEN primary first (78.6%) compared to NEN primary only (67.3%) and non-NEN primary first (66.6%), while NEC histology was more prevalent in NEN only (27.4%) and non-NEN first (29.3%) compared to NEN first. Among patients with NEN first followed by a second primary malignancy (SPM), 23.6% of females had a secondary breast malignancy and 28.9% of males had a secondary prostate malignancy. Conclusions: 28.8% of patients with NENs were found to have OPM, either preceding or following their NEN diagnosis. Of those with a SPM following NEN, breast and prostate were the most common sites for women and men, respectively. It is imperative that patients with NEN undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the timeframe in which they occur in relation to the NEN.

Thymic Carcinomas and Second Malignancies: A Single-Center Review.

Simple SummaryThymic carcinoma (TC) is a rare neoplasm that accounts for less than 0.01% of all tumors. The aim of our retrospective observational analysis is to review the incidence of second cancers associated with this histological type of cancer. We identified 92 patients with TC referred to our consultation practice and reviewed their clinical data for diagnosis of another cancer pre- or post-diagnosis of TC. This resulted in identification of 14 patients with additional cancers. The incidence of second cancer is similar to that observed in thymomas.Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.

Malignancies diagnosed before and after anal squamous cell carcinomas: A SEER registry analysis.

BackgroundIncreased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC.MethodsThis work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population.ResultsA total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs.ConclusionsOur findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies.

Invited Commentary: Secondary Malignancies in Patients Treated with Radiation Therapy.

Invited Commentary: Secondary Malignancies in Patients Treated with Radiation Therapy.