Subsequent Primary Cancers Research Articles

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Risk of developing a subsequent primary cancer among adult cancer survivors.

Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada. We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up. The risk of developing a SPC up to fifteen years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR=1.50) and females (SIR=1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors diagnosed between ages 18-39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPCs among females and males. Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and highlights the need to investigate optimal strategies for screening the growing population of cancer survivors.

Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases.

The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR=1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5years, ≥5years, ≥10years, ≥20years, and ≥30years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR=1.25, P <0.001), endometrial (SIR=1.40, P =0.019), cervical (SIR=2.56, P <0.001), and ovarian cancer (SIR=1.50, P =0.010). FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.

Epidemiology, Pattern, and Survival of Multiple Primary Malignant Neoplasms in Southeast Iran: Results of Kerman Population-Based Cancer Registry 2014-2020.

Cancer survivors may experience a subsequent primary cancer that affects their survival and quality of life. This study aimed to investigate the epidemiology of multiple primary malignant neoplasms (MPMNs) in Kerman province, southeast Iran during 2014-2020. In this retrospective cohort study, all patients who had been diagnosed with primary cancers and registered with the Kerman Cancer Registry Program (KPBCR) during 2014-2020 were included. MPMNs were defined as primary malignant tumors arising in different sites and/or were of different histological or morphological origins. If the second malignancy was diagnosed within the first six months from the diagnosis of the first tumor it was considered synchronous, and if after six months it was defined as metachronous. Logistic regression was used to analyze the relationship between age, sex, and primary cancer site with incidence and survival of secondary in the entire population. Of 26,315 patients registered with a primary cancer diagnosis, 492 (1.86%) developed subsequent primary cancers. The most common type of secondary cancer was skin and mucosa (n=131, 26.63%) followed by urogenital (n=115, 23.37%), followed by, gastrointestinal (n=62, 14.45%), and breast neoplasms (n=57, 11.59%). Most patients had metachronous tumors (n=350, 71.13%). The primary cancer site (Skin and mucosa, urogenital, and breast) was significantly associated with developing subsequent cancer among cancer survivors. The overall 5-year survival of MPMNs cases was over 50%. Older age at diagnosis (HR= 1.02) and having synchronous tumors (HR=1.41) were negatively associated with the survival time of patients with MPMNs. Both patients and physicians should be taught about the importance of prevention and the provision of care and screening services among cancer survivors. Studying the epidemiology, susceptibility, and risk factors of MPMNs among cancer survivors will open windows to a better understanding of this phenomenon and policy making.

The risk for subsequent primary lung cancer after cervical carcinoma: A quantitative analysis based on 864,627 cases.

To compare the risk of developing subsequent primary lung cancer among cervical cancer patients and the general population. Several databases were searched from inception to April 25, 2023. The standard incidence ratios (SIRs) with 95% confidence intervals (CIs) were combined to identify the risk for second primary lung cancer after cervical carcinoma. Subgroup analyses based on the follow-up period, age, degree of malignancy and source of SIR were conducted. All the statistical analyses were performed with STATA 15.0 software. A total of 22 retrospective studies involving 864,627 participants were included. The pooled results demonstrated that cervical cancer patients had a significantly greater risk for lung cancer than did the general population (SIR = 2.63, 95% CI: 2.37-2.91, P<0.001). Furthermore, subgroup analyses stratified by follow-up period (<5 years and ≥5 years), age (≤50 years and <50 years), and degree of malignancy (invasive and in situ) also revealed an increased risk of developing lung cancer among cervical carcinoma patients. Cervical cancer patients are more likely to develop subsequent primary lung cancer than the general population, regardless of age, follow-up time or degree of malignancy. However, more high-quality prospective studies are still needed to verify our findings.

Risk of subsequent primary cancers among adult cancer survivors.

10554 Background: Improvements in early detection and clinical management of cancers have led to a significant increase in long-term cancer survivors who may be at an elevated risk of developing a subsequent primary cancer (SPC). As the largest and most comprehensive analysis in Canada, we assessed the risks and patterns of SPC development among 134,693 adult cancer survivors with 852,661 person-years of follow-up. Methods: We used data from the Alberta Cancer Registry (ACR) to identify all first primary cancers (FPC) occurring between 2004 and 2015 to allow for adequate follow-up until December 31, 2020. A SPC was considered as the next primary cancer occurring in a different organ/site. We estimated incidence rates (IR) and standardized incidence ratios (SIR) for SPC development with 95% confidence intervals (CI). IRs were estimated as the observed number of SPC divided by the person-years of follow-up. SIRs were estimated as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the general population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up among the adult cancer survivors. Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.1% for males and 12.3% for females. These risk estimates varied considerably by initial cancer site. Survivors of initial head and neck cancers had a fifteen-year cumulative incidence of 21.3% and a 2.5-fold relative risk of SPC development. Overall, both males (SIR=1.50) and females (SIR=1.64) had an increased risk of developing a SPC. Both male and female survivors of a FPC were at a significantly increased relative risk of developing a screen-detectable SPC (breast, cervical, colorectal, lung). There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors of early-onset cancers diagnosed between ages 18 to 39. Conclusions: Cancer survivors of nearly every FPC site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and this highlights the need to develop evidence-based guidelines for cancer screening in the growing population of long-term cancer survivors.[Table: see text]

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Abstract LB378: Incidence and trends in subsequent primary lung cancer by sex in the United States

Abstract Importance The difference in lung cancer incidence by sex has been extensively documented in the US. Nonetheless, previous studies did not differentiate between first primary lung cancers (FPLCs) and those that occur in individuals with a history of cancer (i.e., subsequent primary lung cancers or SPLCs). Objective To examine whether the sex-specific pattern in lung cancer incidence rates differ by tumor sequence in the US. Design, Setting, and Participants Lung and bronchus (hereafter, lung) cancer diagnosed from 2001-2020 at ages 20 or older, stratified by sex and tumor sequence (first versus subsequent), were identified from the U.S Cancer Statistics Public Use Database. Main Outcome and Measures Age-standardized (2000 US standard population) incidence rates and female-to-male incidence rate ratio (IRRs) were calculated using SEER*Stat, overall and by age groups (20-49, 50-59, 60-69, 70+ years). Trends in incidence rates were quantified using Joinpoint program, estimating annual percent change (APC). Results From 2001-2020, there were 3,333,495 FPLC diagnoses and 961,130 SPLC diagnoses. For FPLC, the incidence rate in women was 28% lower than in men (57.7 versus 79.8 per 100,000; IRR=0.72, 95%CI=0.72-0.72) with the sex gap greater with increasing age from 0.96 (95%CI=0.95-0.97) in individuals aged 20-49 years to 0.69 (95%CI=0.69-0.70) in those aged 70 years or older. For SPLC, the incidence rate in women was 33% lower than in men (17 versus 25 per 100,000; IRR=0.67, 95%CI=0.67-0.68). However, the lower incidence of SPLC in women was seen only among people aged 60 or older. Intriguingly, the incidence rate of SPLC in women was twice as high as in men among those aged 20-49 years (0.83 versus 0.44 per 100,000; IRR=1.90, 95%CI=1.83-1.96) and 25% higher among those aged 50-59 years (11.05 versus 8.84 per 100,000; IRR=1.25, 95%CI=1.23-1.27). From 2001-2019, incidence rates of FPLC decreased for both men (1.88% to 3.45% per year) and women (1.23% to 2.24% per year), although the decrease began in 2006 in women. For SPLC, the incidence rate in men showed a 2.74% annual increase from 2001-2007, followed by a decrease (APC=-1.91%, 95%CI=-2.27 to -1.68) from 2012-2019, while the incidence rate in women exhibited a 4.05% annual increase from 2001-2009, followed by a continued increase at a slower pace (APC=0.48%, 95%CI=0.28-0.69). The rising trends in SPLC among women were primarily driven by those aged 50 or older. In particular, the incidence rate of SPLC among women aged 70 or older increased by 5.4% per year from 2001-2009, followed by a 0.92% annual increase from 2009-2019. Conclusion Sex-specific patterns in lung cancer incidence differ considerably between first versus subsequent primary lung cancer. The findings highlight variations in sex-specific exposures within different populations at risk such as the general population versus cancer survivors. Further research is needed to identify reasons for the female predominance of SPLC among young adults and the concerning rise of SPLC rates in women. Citation Format: Hyuna Sung, Chenxi Jiang, Priti Bandi, Elizabeth Schafer, Farhad Islami, Ahmedin Jemal. Incidence and trends in subsequent primary lung cancer by sex in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB378.

Abstract LB151: Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States

Abstract Background Breast cancer survivors face an elevated risk of subsequent primary lung cancer (SPLC), especially those who received radiotherapy. Nevertheless, the association of radiotherapy for breast cancer and the risk of subtype-specific lung cancer is unknown. Methods Females diagnosed with first primary breast cancer at ages 20-84 years from 1992-2020 were identified from 12 Surveillance, Epidemiology, and End Results registries. Follow-up began at 2 months from breast cancer diagnosis and ended at subsequent lung cancer diagnosis, last known vital status, death, or December 31, 2020. Standardized incidence ratios (SIRs) and excess absolute risks (EARs, per 10,000 women) were calculated for each histological subtype of lung cancer (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, and others) using expected rates of each subtype in the SEER population. Subgroup analyses were conducted by treatment for breast cancer (radiotherapy yes or no/unknown), overall and stratified by the relative position (ipsilateral and contralateral) of the breast and SPLC. Results Of all 550,007 breast cancer survivors (&amp;gt;50 years old, 74%; non-Hispanic Whites, 67%; localized, 51%), 8,014 SPLCs were diagnosed during a mean follow-up of 9.7 years. 52.6% of the participants received radiotherapy treatment. Compared with the general population, breast cancer survivors had a statistically significantly higher risk of lung cancer with subtype-specific SIR being greatest for adenocarcinoma (Observed N=4337; SIR=1.20, 95% Confidence Interval [CI]=1.16-1.24; EAR=1.35), followed by squamous cell carcinoma (Observed N=1368; SIR=1.11, 95% CI=1.05-1.17; EAR=0.26) and small cell carcinoma (Observed N=1026; SIR=1.08, 95% CI=1.02-1.15; EAR=0.14). When stratified by radiotherapy receipt, the increased risk associated with adenocarcinoma did not vary across strata. In contrast, the increased risk for squamous and transitional cell carcinoma and small cell carcinoma were confined to those who received radiotherapy (SIR=1.16, 95% CI=1.08-1.24 vs SIR=1.06, 95% CI=0.98-1.15 for squamous and transitional cell carcinoma; SIR=1.15, 95% CI=1.06-1.25 vs SIR= 1.00, 95% CI=0.91-1.09 for small cell carcinoma). Further analysis by laterality showed that associations of treatment receipt with increased risk of lung cancer were confined to ipsilateral SPLC for these two subtypes. Conclusion Different subtypes of lung cancer may have distinct associations with prior radiation treatment in individuals who have survived breast cancer. The findings have implications for evaluating risks and implementing surveillance for subsequent primary lung cancer in the growing population of breast cancer survivors. Citation Format: Chenxi Jiang, Rachel A. Freedman, Ahmedin Jemal, Hyuna Sung. Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB151.

Primary carcinoma esophagus with unusual synchronous second malignancies: A case series

Multiple primary cancer is no longer a rarity. As life expectancy has increased, more individuals are living long enough to develop not only one but also two or more cancers. Herein, we report on three cases of synchronous malignancies associated with the primary esophagus cancer. All three patients posed a challenge for the treatment. These patients carry a dismal prognosis so early diagnosis of subsequent cancer at a curable stage by regular follow-up is encouraged. The early investigation of new symptoms and signs may help to diagnose, initiate early treatment, and reduce the number of deaths from subsequent primary cancers in patients.

Avoiding lead-time bias by estimating stage-specific proportions of cancer and non-cancer deaths

PurposeUnderstanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening.MethodsUsing data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50–84 years at cancer diagnosis in 2006–2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020.ResultsMost cancer patients diagnosed at stages I–II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I–II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I–II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach.ConclusionAcross all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I–II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened.

Factors associated with the onset and survival of subsequent primary breast cancer in female non‐metastatic breast cancer survivors

AbstractThis study aimed to investigate the risk factors for the onset of subsequent primary breast cancer (SPBC) in women with a previous diagnosis of early‐stage breast cancer (BC) and to construct a prognostic prediction model for patients with SPBC. Using the Surveillance, Epidemiology, and End Results‐17 (SEER‐17) database, we conducted a retrospective cohort analysis on women with initial primary early‐stage BC from 2004 to 2015. Standardized incidence ratio (SIR) was calculated to determine the risk of subsequent primary cancer (SPC). A competing risk model was built to identify the risk factors for the onset of SPBC. And risk factors associated with breast cancer‐specific mortality in SPBC patients were evaluated and presented in the form of nomogram. Compared with the general population, the overall risk of SPC for all sites was significantly elevated in women with early‐stage BC (SIR = 1.21, 95% CI: 1.20–1.23), and breast is the most frequent site. Age, race and ethnicity, year of diagnosis, history of other tumors, histological type, surgery, radiation, chemotherapy, tumor size, positive lymph nodes numbers and ER status were independent risk factors (p &lt; .05) for the onset of SPBC. A new prognosis nomogram demonstrated good discrimination after internal validation with a C‐index of 0.869 (95% CI: 0.859–0.880), and showed favorable consistency and clinical usefulness. The incidence of SPBC and prognosis of patients with SPBC were well estimated based on a large cohort. Our nomogram model had excellent prediction performance and could be a useful tool to predict prognosis.

Discussion to: Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer

Discussion to: Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer

Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer

BackgroundRadiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3 decades to quantify this risk over time as modern oncologic treatment continues to evolve. MethodsThe SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9 years, 10 to 15 years, and >15 years after breast cancer diagnosis. ResultsOf the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P = .036) after 5 to 9 years of follow-up, 1.28 (P = .002) after 10 to 15 years of follow-up, and 1.30 (P = .014) after >15 years of follow-up. The HR of contralateral lung cancer was not increased at any time interval. ConclusionsThe increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

Risk of Subsequent Primary Cancer in Thyroid Cancer Survivors: A Nationwide Population-Based Study.

Background: Despite obtaining a good prognosis and long life expectancy, survivors of thyroid cancer can nevertheless develop subsequent primary cancer (SPC). We investigated the risk and types of SPC in patients with thyroid cancer and compared them with subjects without thyroid cancer history (controls). Methods: We conducted a nationwide, population-based, retrospective cohort study based on the Korean National Health Insurance Database. A total of 432,654 patients diagnosed with thyroid cancer between 2004 and 2019 were 1:1 matched with controls for age, sex, income, and region of residence. The hazard ratios (HR) and 95% confidence intervals (CI) of SPC were estimated using Cox proportional hazard models. Results: In total, 78,584 (18.2%) patients with thyroid cancer and 49,979 (11.6%) controls were diagnosed with SPCs over a mean follow-up of 6.9 years. Patients with thyroid cancer had a higher risk of SPC at any site (adjusted HR, 1.62; 95% CI, 1.60-1.64) than the controls. The risk of SPCs was particularly high for patients diagnosed with thyroid cancer at a younger age (<40 years) and within 5 years. Conclusions: Medical caregivers should consider the long-term follow-up of patients with thyroid cancer and discuss the risk of SPC, especially if they complain of cancer-related symptoms.

A metachronous second primary lung cancer after laryngectomy for laryngeal carcinoma.

A combination of laryngeal carcinoma and subsequent primary lung cancer is rare yet important in terms of therapeutic strategy and prognosis.

Association of first primary cancer with risk of subsequent primary cancer among survivors of adult-onset cancers in Kentucky and Appalachian Kentucky.

Appalachia is a region with significant cancer disparities in incidence and mortality compared to Kentucky and the United States. However, the contribution of these cancer health disparities to subsequent primary cancers (SPCs) among survivors of adult-onset cancers is limited. This study aimed to quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types, residence and sex. This retrospective cohort study from the Kentucky Cancer Registry included 148,509 individuals aged 20-84 years diagnosed with FPCs from 2000-2014 (followed until December 31, 2019) and survived at least 5 years. Expected numbers of SPC were derived from incidence rates in the Kentucky population; standardized incidence ratio (SIR) compared with those expected in the general Kentucky population. Among 148,509 survivors (50.2% women, 27.9% Appalachian), 17,970 SPC cases occurred during 829,530 person-years of follow-up (mean, 5.6 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 30 FPC types, as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 31 FPC types, as compared to the general population. The highest overall SIR were estimated among oral cancer survivors (SIR, 2.14 [95% CI, 1.97-2.33] among men, and among laryngeal cancer survivors (SIR, 3.62 [95% CI, 2.93-4.42], among women. Appalachian survivors had significantly increased risk of overall SPC and different site specific SPC when compared to non-Appalachian survivors. The highest overall SIR were estimated among laryngeal cancer survivors for both Appalachian and non-Appalachian residents (SIR, 2.50: 95%CI, 2.10-2.95; SIR, 2.02: 95% CI, 1.77-2.03, respectively). Among adult-onset cancer survivors in Kentucky, several FPC types were significantly associated with greater risk of developing an SPC, compared with the general population. Risk for Appalachian survivors was even higher when compared to non-Appalachian residents, but was not explained by higher risk of smoking related cancers. Cancers associated with smoking comprised substantial proportions of overall SPC incidence among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Alberta Childhood Cancer Survivorship Research Program.

Adverse outcomes after childhood cancer have been assessed in a range of settings, but most existing studies are historical and ascertain outcomes only after 5-year survival. Here, we describe the Alberta Childhood Cancer Survivorship Research Program and its foundational retrospective, population-based cohort of Albertan residents diagnosed with a first primary neoplasm between the ages of 0 and 17 years from 1 January 2001 to 31 December 2018. The cohort was established in collaboration with the Alberta Cancer Registry and Cancer in Young People in Canada program and has been linked to existing administrative health databases and patient-reported outcome questionnaires. The cohort comprised 2580 survivors of childhood cancer, 1379 (53.4%) of whom were 5-year survivors. Approximately 48% of the cohort was female, 47% of the cohort was diagnosed between 0 and 4 years of age, and the most frequent diagnoses were leukemias (25.4%), central nervous system tumors (24.0%), and lymphomas (14.9%). Detailed treatment information was available for 1741 survivors (67.5%), with manual abstraction ongoing for those with missing data. By the study exit date, the median time since diagnosis was 5.5 years overall and 10.4 years for 5-year survivors. During the follow-up time, 82 subsequent primary cancers were diagnosed, 20,355 inpatient and 555,425 ambulatory/outpatient events occurred, 606,773 claims were reported, and 437 survivors died. The results from this research program seek to inform and improve clinical care and reduce cancer-related sequelae via tertiary prevention strategies.

Racial and ethnic disparities in survival among persons with subsequent primary cancer.

12093 Background: Racial and ethnic disparities in survival after first primary cancer diagnoses have been well documented. Yet comprehensive data for disparities after subsequent primary cancer (SPC) are lacking despite the growing burden of SPCs. Methods: This study included 230,370 persons diagnosed with one of the 13 common SPCs at ages≥20 years during 2000-2013 in 18 Surveillance, Epidemiology, and End Results registries. Cause-specific proportional hazards models were used to estimate HR (hazard ratio), overall and stratified by SPC types, comparing the risk of cancer or cardiovascular death in Hispanic, non-Hispanic Asian or Pacific Islander (API), or non-Hispanic Black (Black) persons to that in non-Hispanic White (White) persons. HRs were adjusted for sex, first primary cancer type and stage, age and year of SPC diagnosis (base model); and additionally household income, urbanicity, SPC stage, subtype, and treatment receipt (surgery, radiotherapy, chemotherapy) (final model). Results: During 54 months of median follow-up, 109,757 cancer deaths and 18,283 cardiovascular deaths occurred among persons with SPCs. Overall, HRs for cancer death were higher among Black (HR = 1.21, 95% CI = 1.18-1.23) and Hispanic (HR = 1.10, 95% CI = 1.07-1.13) persons compared with White persons, but lower among API persons (HR = 0.93, 95% CI = 0.90-0.96) in the base model. When stratified by SPC types, the increased HRs were evident for 10 of 13 cancers among Black persons with the greatest HR among those with uterine corpus cancer (HR = 1.87, 95%CI = 1.63-2.15) and for 7 of 13 cancers among Hispanic persons with the highest HR among those with melanoma (HR = 1.46, 95%CI = 1.21-1.76). For cardiovascular death, compared with White persons, the overall HR was higher among Black (HR = 1.42, 95% CI = 1.35-1.49) persons but lower among API (HR = 0.75, 95%CI = 0.69-0.81) and Hispanic (HR = 0.90, 95% CI = 0.84-0.96) persons. The risk of cardiovascular death was higher for 11 of 13 cancers among Black persons with the greatest HR among those with pancreatic (HR = 1.80, 95%CI = 1.17-2.75), thyroid (HR = 1.70, 95%CI = 1.12-2.57), and kidney (HR = 1.63, 95%CI = 1.38-1.93) cancers. Additional adjustments in the final model reduced the elevated HRs substantially especially for cancer death among Black or Hispanic persons, although the associations remained statistically significant for most cancers. Conclusions: Among persons with SPCs, Black persons had a higher risk of death from both cancer and cardiovascular disease, whereas Hispanic persons had a higher risk of death from cancer. Adjusting for differences in potentially modifiable factors attenuated the associations substantially, highlighting opportunities for interventions toward health equities among cancer survivors.