Risk of Second Primary Malignancies in Chronic Lymphocytic Leukemia

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, with ~21,000 estimated new cases in 2018. Prior retrospective studies have suggested an increased risk of second primary malignancies (SPMs) in CLL patients. Population-based studies on the risk of SPMs in CLL are limited, especially in the last decade with improvements in prognostic and therapeutic tools over the last decade. As the survival of CLL patient improves, it may lead to more survivors who are at risk of developing SPMs. In this study, we sought to evaluate the risk of development of SPMs among CLL patients diagnosed from 2000-2014. Methods: We used the SEER 18 registries for the calculation of risk of SPMs and included CLL cases that were confirmed histologically between 2000-2014 (https://seer.cancer.gov/). SPMs diagnosed within 2 months of primary CLL diagnosis were excluded. Time to SPM was calculated by subtracting second malignancy survival/follow-up time from CLL survival/follow-up time. The SEER*Stat Multiple Primary-SIR tool was used to calculate SIRs for secondary malignancies by comparing these patients' subsequent cancer experience with the number of cancers that would be expected based on incidence rates for the general U.S. population. These analyses were adjusted for age, gender, race, and year of CLL diagnosis. Multivariate logistic regression was performed to identify factors associated with development of SPM. Results: The study cohort included 46,164 patients with CLL. After a median follow up of 50 months (range 1-179), 5220 (11.3%) patients developed a total of 5,738 subsequent malignancies. As compared to that of general population, CLL patients had a higher risk of developing SPMs (SIR: 1.40 [95%CI:1.37-1.44]) and the risk was much higher for hematologic malignancies (SIR: 2.63 [95%CI:2.47-2.80]) as compared to solid organ malignancies (SIR: 1.25 [95%CI: 1.22-1.29]). In addition to known common SPMs in CLL (lymphoma, melanoma, lung cancer, and prostate cancer), there was an elevated risk of developing acute lymphoblastic leukemia (SIR 5.43), chronic myeloid leukemia (SIR 2.18), thyroid cancer (SIR 2.09), and kidney cancer (SIR 1.70) (Table). Out of the 5220 patients who developed SPMs, 437 (8.3%) patients developed two subsequent second primary malignancies, and 81 (1.5%) patients developed > 2 subsequent primary cancers, which was significantly more than the endemic rate (SIR, 1.40; p <.05). Of the 5738 SPMs, 1095 (19%) occurred in 2-11 months, 2822 (49%) in 1-5 years, 1499 (26%) in 6-10 years and 321 (6%) beyond 10 years of CLL diagnosis (Figure). On logistic regression, males had higher odds of developing SPMs than females (OR: 1.46 [95% CI: 1.38-1.56], p<0.0001) and the patients diagnosed with from 2000-2007 had higher odds of developing SPMs as compared to those diagnosed from 2007-2014 (OR: 2.28 [95%CI: 2.15-2.42], p<0.0001]. The risk of developing SPM did not differ based on the age, race and between the patients who received first line therapy and no initial therapy. CLL patients who developed SPMs had significantly less median overall survival as compared to that of patients who did not develop SPMs (93 vs 109 months, p<0.05). Conclusion: In this large population-based study, CLL patients had an elevated risk of developing second primary hematologic and solid malignancies. The specific types of SPMs were varied, ranging from common ones such as lymphoma, lung cancer, prostate cancer, to uncommon ones such as thyroid cancer, kidney cancer, and chronic myeloid leukemia. The patients who were diagnosed after 2007 had a lower risk of developing SPMs as compared to those diagnosed before. There is a need for studies evaluating immunological repertoire of CLL and its impact on development of SPMs. Knowledge of these SPMs may help physicians with their early detection. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Second primary malignancies in gastric cancer: A U.S. population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.191 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 191-191

Author(s):

Binay Kumar Shah ◽

Amit Khanal

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Gastric Cancer ◽

Thyroid Cancer ◽

Myeloid Leukemia ◽

Population Based ◽

Second Primary ◽

Population Based Study ◽

Gastrointestinal Malignancies ◽

Second Primary Malignancies

191 Background: Risk of second primary malignancies (SPM) is not known in gastric cancer. In this population based study, we analyzed rates of SPM in gastric cancer. Methods: We selected adult (≥18 years) patients with gastric cancer as first primary malignancy diagnosed from January 1992 to December 2011 from Surveillance, Epidemiology and End Result 13 database. We used SEER*stat’s multiple primary standardized incidence ratio (MP-SIR) session to calculate the risk of SPM diagnosed 6 months after the diagnosis of index gastric cancer. Results: Among 31,818 patients with first primary gastric cancer, 1674 (5.26%) developed 1,839 SPM with observed/expected (O/E) ratio of 1.09 (95% CI = 1.05-1.15, p<0.0001) and excess risk of 16.15 per 10,000 population. The median time to first SPM from the time of diagnosis of stomach cancer was 49 months (range 6 months to 19.08 years). There was significantly increased risk of gastrointestinal malignancies [O/E ratio 1.65 (CI=1.53-1.79, p<0.001)], thyroid cancer [O/E ratio 1.98 (CI=1.32-2.84, p<0.01)] and myeloid leukemia [O/E ratio 1.47(CI=1-2.09, p<0.05)]. Interestingly, there was significantly decreased risk of melanoma, breast cancer and prostate cancer. Conclusions: Our study showed that patients with gastric cancer are at higher risk of gastrointestinal malignancies, thyroid cancer and myeloid leukemia. Similarly, risk of melanoma, breast cancer and prostate cancer in patients with gastric cancer is lower than general population.

Download Full-text

Second primary malignancies following thyroid cancer: a population-based study in Taiwan

Acta Endocrinologica ◽

10.1530/eje-13-0309 ◽

2013 ◽

Vol 169 (5) ◽

pp. 577-585 ◽

Cited By ~ 20

Author(s):

Chang-Hsien Lu ◽

Kuan-Der Lee ◽

Ping-Tsung Chen ◽

Chih-Cheng Chen ◽

Feng-Che Kuan ◽

...

Keyword(s):

Thyroid Cancer ◽

Large Scale ◽

Negative Impact ◽

Asian Population ◽

Population Based ◽

Second Primary ◽

Population Based Study ◽

Impact On Survival ◽

Second Primary Malignancies

ObjectiveMost studies on second primary malignancies (SPMs) after primary thyroid cancer were conducted in USA or Europe. The discrepancy between SPMs in these studies could be attributed to geographical and ethnic heterogeneity. Thus, there is a clear need for another large-scale epidemiological study, particularly in Asian countries, to define the incidence and risk of SPMs in thyroid cancer survivors.DesignA population-based study was conducted using the nation-wide database from Taiwan Cancer Registry between 1979 and 2006.MethodsWe quantified standardized incidence ratios (SIRs) and cumulative incidence of SPMs among 19 068 individuals (4205 males and 14 863 females) with primary thyroid cancer.ResultsA total of 644 cases (3.38%) developed at least a SPM during 134 678 person-years of follow-up. The risk for subsequent SPMs was significantly greater than that of the general population (SIR=1.33, 95% CI 1.23–1.44). There was a greater risk of developing major salivary glands, nasopharyngeal, lung, thymus, breast (females), bladder, and brain cancers, and leukemia and lymphoma. We observed that the risk was highest within the first 5 years of diagnosis of thyroid cancer (SIR=5.29, 1.68, and 0.68 for ≦5, 5–10, and >10 respectively) and in the younger patients (SIR=1.81 vs 1.61 for <50 and ≧50 respectively). The median overall survival for primary thyroid cancer patients was 23.28 years, but it was only 4.73 years for those who developed SPMs.ConclusionThyroid cancer is associated with a 33% risk increment of SPMs, which had a negative impact on survival. There are sites of SPMs in the Asian population that are distinctive from those in the Western population, suggesting that other genetic predisposition or environmental factors may play a role.

Download Full-text

Second Hematologic Malignancies After Radioiodine Exposure In Patients With Thyroid Cancer and The Relationship With Radioiodine Dosage: A Nationwide Population-Based Study

Blood ◽

10.1182/blood.v122.21.1375.1375 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1375-1375

Author(s):

Chia-Jen Liu ◽

Man-Hsin Hung ◽

Chung-Jen Teng ◽

Yu-Wen Hu ◽

Yi-Ping Hung ◽

...

Keyword(s):

Thyroid Cancer ◽

Dose Response ◽

Hematologic Malignancies ◽

Population Based ◽

Second Primary ◽

Population Based Study ◽

Increased Risk ◽

Clear Dose Response ◽

Second Primary Malignancies

Abstract Background Second primary malignancies are one of the most important late effects after radioactive iodine (RAI) exposure, which is widely used in the diagnosis and treatment for thyroid cancers. However, dose-response correlation between RAI and second hematologic malignancies (SHM) was not established. Therefore, we conducted a nationwide population-based study to investigate the risk of SHM among thyroid cancer patients and the association between RAI dosage and development of SHM, including leukemia. Material and methods We recruited patients with newly diagnosed thyroid cancer aged 20 years or older without antecedent cancer from the Taiwan National Health Insurance database between 1997 and 2010. The standardized incidence ratios (SIR) of cancers were calculated to compare the cancer incidence of thyroid cancer patients to the general population according to gender, calendar year, and age in 5-year intervals by the corresponding stratum-specific person-time accrued in the cohort. The association of cumulative RAI dosage and development of SHM, including leukemia, was estimated using time-dependent analysis with 2-year latent period. Results After exclusion of first-year follow-up, 692 second primary malignancies developed among 20,235 patients with thyroid cancer, with a follow-up of 134,178 person-years. Fifty SHM developed with a SIR of 2.37 (95% confidence interval 1.76-3.13). The significant increased risk of SHM included: leukemia (SIR, 2.74; 95% CI, 1.65-4.28), non-Hodgkin lymphoma (SIR, 2.38; 95% CI, 1.55-3.48). As a time-dependent covariate with a 2-year latent period, RAI significantly increased the risk of leukemia with a clear dose-response correlation (age- and sex-adjusted hazard ratio per 100 mCi increase, 1.10; 95% CI, 1.01-1.19, P = 0.032). This effect was not seen in other second primary malignancies. Conclusions Our study reveals increased risk of SHM among patients with thyroid cancer. RAI increases the risk of leukemia with a clear dose-response relationship. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia

Blood Cancer Journal ◽

10.1038/s41408-019-0237-1 ◽

2019 ◽

Vol 9 (10) ◽

Cited By ~ 5

Author(s):

Vivek Kumar ◽

Sikander Ailawadhi ◽

Leyla Bojanini ◽

Aditya Mehta ◽

Suman Biswas ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Hematological Malignancies ◽

Lymphocytic Leukemia ◽

Second Primary ◽

Standardized Incidence Ratio ◽

Improved Outcomes ◽

History Of ◽

Second Primary Malignancies

Abstract With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.

Download Full-text

Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States

Prostate Cancer ◽

10.1155/2019/4387415 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Catherine W. Saltus ◽

Zdravko P. Vassilev ◽

Jihong Zong ◽

Brian Calingaert ◽

Elizabeth B. Andrews ◽

...

Keyword(s):

Prostate Cancer ◽

United States ◽

Cohort Study ◽

Incidence Rate ◽

Retrospective Cohort ◽

Population Based ◽

Second Primary ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Second Primary Malignancies

Background. New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival. Methods. We conducted a retrospective cohort study of United States (US) men aged ≥ 65 years with CRPC. Cohort entry was from January 1, 2000, to December 31, 2011, with follow-up through December 31, 2013. Castration resistance was defined by treatment with second-line systemic therapy (after surgical or medical castration). SPM were diagnoses of primary cancers (other than prostate) in SEER or Medicare data. Results. Altogether 2,234 patients met eligibility criteria. Most (1,887; 84.5%) had evidence of bone metastases in Medicare claims. SPM occurred in 172 patients (incidence rate 5.9 per 100 person-years; 95% confidence interval [CI], 5.0-6.8; standardized incidence ratio = 3.1, 95% CI, 2.8-3.6, based on SEER incidence rate of all malignancies except prostate cancer among men aged ≥ 65 years). The most common SPM were lung/bronchus (n = 29, 16.9%), urinary bladder (n = 22, 12.8%), and colon/rectum (n = 21, 12.2%). Median survival was 1.2 years (95% CI, 1.1-1.3); 5-year survival was 9% (95% CI, 7-11%). Conclusions. This study provides the first estimate of SPM risk in older men with CRPC in the US. The incidence rate is approximately threefold higher than the population-based cancer incidence among men without prostate cancer.

Download Full-text

Impact Of Restriced Follow-Up Times In Clinical Trials On Overall Survival Estimates: A Case Comparison Of Advanced Prostate Cancer, Advanced Lung Cancer, And Chronic Myeloid Leukemia Using Registry Data

Value in Health ◽

10.1016/j.jval.2016.03.1708 ◽

2016 ◽

Vol 19 (3) ◽

pp. A98

Author(s):

D Shah ◽

V Paly ◽

M Sidhu ◽

A Briggs

Keyword(s):

Prostate Cancer ◽

Lung Cancer ◽

Overall Survival ◽

Clinical Trials ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Advanced Prostate Cancer ◽

Advanced Lung Cancer ◽

Case Comparison

Download Full-text

Previous Extrapulmonary Malignancies Impact Outcomes in Patients With Surgically Resected Lung Cancer

Frontiers in Surgery ◽

10.3389/fsurg.2021.747249 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hsin-Ying Lee ◽

Min-Shu Hsieh ◽

Hsien-Chi Liao ◽

Pei-Hsing Chen ◽

Xu-Heng Chiang ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Thyroid Cancer ◽

Medical Records ◽

Primary Lung Cancer ◽

Clinicopathological Parameters ◽

Second Primary ◽

Patients With Cancer ◽

History Of ◽

Second Primary Malignancies

Background: As the overall survival of patients with cancer continues to improve, the incidence of second primary malignancies seems to be increasing. Previous studies have shown controversial results regarding the survival of patients with primary lung cancer with previous extrapulmonary malignancies. This study aimed to determine the clinical picture and outcomes of this particular subgroup of patients.Materials and Methods: We included 2,408 patients who underwent pulmonary resection for primary lung cancer at our institute between January 1, 2011 and December 30, 2017 in this retrospective study. Medical records were extracted and clinicopathological parameters and postoperative prognoses were compared between patients with lung cancer with and without previous extrapulmonary malignancies.Results: There were 200 (8.3%) patients with previous extrapulmonary malignancies. Breast cancer (30.5%), gastrointestinal cancer (17%), and thyroid cancer (9%) were the most common previous extrapulmonary malignancies. Age, sex, a family history of lung cancer, and preoperative carcinoembryonic antigen levels were significantly different between the two groups. Patients with previous breast or thyroid cancer had significantly better overall survival than those without previous malignancies. Conversely, patients with other previous extrapulmonary malignancies had significantly poorer overall survival (p < 0.001). The interval between the two cancer diagnoses did not significantly correlate with clinical outcome.Conclusion: Although overall survival was lower in patients with previous extrapulmonary malignancies, previous breast or thyroid cancer did not increase mortality. Our findings may help surgeons to predict prognosis in this subgroup of patients with primary lung cancer.

Download Full-text

Syncope as a sign of occult cancers: a population-based cohort study

British Journal of Cancer ◽

10.1038/s41416-019-0692-2 ◽

2019 ◽

Vol 122 (4) ◽

pp. 595-600

Author(s):

Mads Okkels Birk Lorenzen ◽

Dóra Körmendiné Farkas ◽

Kasper Adelborg ◽

Jens Sundbøll ◽

Henrik Toft Sørensen

Keyword(s):

Prostate Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Brain Cancer ◽

Cumulative Risk ◽

Population Based ◽

Occult Cancer ◽

Cumulative Risks ◽

Syncope Episode

Abstract Background We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population. Methods Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994–2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI). Results Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1–20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4–3.0) for lung cancer, 2.0 (95% CI: 1.8–2.2) for colorectal cancer, 1.7 (95% CI: 1.5–1.9) for prostate cancer and 10.0 (95% CI: 8.6–11.4) for brain cancer. Conclusions Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted.

Download Full-text

The Risk of Second Primary Malignancies up to Three Decades after the Treatment of Differentiated Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1154 ◽

2008 ◽

Vol 93 (2) ◽

pp. 504-515 ◽

Cited By ~ 221

Author(s):

Aaron. P. Brown ◽

Jergin Chen ◽

Ying J. Hitchcock ◽

Aniko Szabo ◽

Dennis C. Shrieve ◽

...

Keyword(s):

Thyroid Cancer ◽

General Population ◽

Differentiated Thyroid Cancer ◽

Second Primary ◽

Second Primary Cancers ◽

Increased Risk ◽

Absolute Excess Risk ◽

Second Primary Malignancies ◽

Radioisotope Therapy

Abstract Background: The 10-yr survival rate of patients with differentiated thyroid cancer exceeds 90%. These patients may be at elevated risk for secondary cancers. Methods: The risk of nonthyroid second primary malignancies after differentiated thyroid cancer was determined in 30,278 patients diagnosed between 1973 and 2002 from centers participating in the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. Median follow-up was 103 months (range, 2–359 months). Risk was further assessed for the addition of radioisotope therapy, gender, latency to development of secondary cancer, and age at thyroid cancer diagnosis. Results: There were 2158 patients who developed a total of 2338 nonthyroid second primary malignancies, significantly more than that expected in the general population [observed/expected (O/E) = 1.09; 95% confidence interval (CI), 1.05–1.14; P < 0.05; absolute excess risk per 10,000 person-years (AER) = 6.39]. A significantly greater risk of second primary malignancies over that expected in the general population was for patients treated with radioisotopes (O/E = 1.20; 95% CI, 1.07–1.33; AER = 11.8) as well as for unirradiated patients (O/E = 1.05; 95% CI, 1.00–1.10; AER = 3.53). However, the increased risk was greater for the irradiated vs. the unirradiated cohort (relative risk = 1.16; 95% CI, 1.05–1.27; P < 0.05). Gender did not affect risk. The greatest risk of second primary cancers occurred within 5 yr of diagnosis and was elevated for younger patients. Conclusions: The overall risk of second primary malignancies is increased for thyroid cancer survivors and varies by radioisotope therapy, latency, and age at diagnosis.

Download Full-text