Second Primary Cancer Research Articles

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data.

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.

Health-promoting behaviors among middle-aged breast cancer survivors compared with matched non-cancer controls: A KNHANES VI-VII (2013-2018) study.

This study aimed to compare health-promoting behaviors between middle-aged breast cancer survivors and matched non-cancer controls. We conducted a retrospective, cross-sectional, matched case-control study using data from Korean National Health and Nutrition Examination Surveys (KNHANES) VI-VII (2013-2018) to compare health-promoting behaviors. We selected breast cancer survivors aged 40 to 65 who completed the surveys, and each case was matched with 5 non-cancer controls (1:5) based on propensity scores. With multivariable logistic regression, middle-aged breast cancer survivors were compared with controls in terms of their last screening for a second primary cancer (SPC), current smoking status, alcohol consumption, aerobic physical activity (PA), sedentary time, and self-reported diet control. The final study sample consisted of 117 middle-aged breast cancer survivors and 585 non-cancer controls after propensity score matching (PSM). In the multivariable analysis, middle-aged breast cancer survivors were less likely to consume alcohol (odds ratio [OR] 0.58, 95% confidence interval [CI], 0.35-0.95), more likely to engage in aerobic PA (OR, 1.60; 95% CI, 1.01-2.54), and more likely to self-report diet control (OR, 2.12; 95% CI, 1.27-3.53). There were no significant intergroup differences in SPC screening uptake within 2 years, smoking status, or sedentary times. There is a need to educate middle-aged breast cancer survivors about SPC screening, smoking cessation, and minimizing sedentariness to reduce the risks of associated with breast cancer recurrence, SPCs, and comorbid chronic diseases.

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors

BackgroundLung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. Patients and methodsThis retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. ResultsAmong the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min–max: 7–173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27–0.58). ConclusionTreatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Second primary cancers and survival among neuroendocrine tumor patients.

There is an increased risk of second primary cancers (SPCs) after neuroendocrine tumor (NET) diagnosis. The clinical significance of SPCs in this population is unknown. The purpose of this study was to evaluate the association between SPCs after NET diagnosis and survival. We performed a population-based, retrospective cohort study of NET patients (gastrointestinal, pancreatic, or lung primary) from 2000-2016 using the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression models assessed the association between SPCs and NET-specific (NET-SS), cancer-specific (CSS), and overall survival (OS). Of 58,553 NET patients, 7.9% experienced a SPC. SPCs were associated with worse OS (HR 2.14, 95%CI 1.94-2.36) and CSS (HR 2.31, 95%CI 2.06-2.59) with no difference in NET-SS (HR 1.04, 95%CI 0.87-1.23). Stratified analyses by histologic grade showed similar results for well and moderately differentiated NETs, but no difference in OS or CSS for poorly differentiated NETs (p>0.05). In stratified analyses by NET site, SPCs were associated with worse OS (HR 3.41, 95%CI 3.01-3.87) and CSS (HR 4.96, 95%CI 4.28-5.74) in gastrointestinal NETs and worse OS (HR 1.25, 95%CI 1.03-1.52) with no difference in CSS (HR 1.08, 95%CI 0.85-1.36) in lung NETs. SPCs were not associated with a difference in OS or CSS in pancreatic NETs (p>0.05). In conclusion, SPCs after NETs were associated with inferior OS and CSS compared to no SPC, but were not associated with NET-SS. These data highlight the need for long-term follow-up in NETs to include detection of SPCs to ensure early diagnosis and timely management.

Second primary cancers in people with HIV/AIDS: a national data linkage study of incidence and risk factors.

The evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. We performed a national population-based data linkage study to determine the incidence and risk factors for SPC in PLWHIV in Australia between 1982 and 2012. We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality and CD4+ count. Of 29,383 individuals diagnosed with HIV, 3,123 who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n=71, 31%). The incidence of SPC overall did not change over time, however there was an increase in individuals diagnosed with HIV in later eras (p-trend=0.001). The incidence of non-infection related SPC increased over time and was associated with older age (p-trend=0.005) and the acquisition of HIV in later eras (p-trend <0.001). Conversely, the incidence of infection-related SPC decreased (p-trend <0.001), but this was no longer significant after adjustment for age (p-trend=0.14). The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection related cancer, likely due to ageing of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Clinical characteristics and prognostic nomogram analysis of patients with dual primary cancers with first gastric cancer: a retrospective study in China.

With the improvement in diagnosis and treatment of gastric cancer (GC), the survival time of patients has been gradually prolonged. However, these survivors are at increased risk for other diseases, including second primary cancers (SPCs). Currently, there remain few central studies concerning double primary cancers with first gastric cancer (DPCFGC). Thus, this study aimed to investigate these patients' clinical characteristics and perform prognostic nomogram analysis. The clinical data of 78 DPCFGC patients were retrospectively collected and analyzed through the hospital electronic medical record system. Univariate and multivariate Cox regression analyses were performed to screen independent risk factors, based on which the prognostic nomogram was further constructed and validated using the R software package. Finally, Kaplan-Meier curves were plotted to explore the association of overall survival (OS) with prognostic factors and the model. The prevalence of DPCFGC was 0.86%, of which the proportions of synchronous and metachronous patients were 47.44% and 52.56% , respectively; 65.38% (51/78) and 34.62% (27/78) of patients were male and female, respectively. The median age at GC and SPC diagnosis was 63 and 65 years, respectively, and 52.57% of GC patients developed SPCs within 1 year. The top three SPCs were in the esophagus (19.24%), colon (16.67%), and rectum (15.39%). The most common features of GC and SPCs were adenocarcinoma, poorly and moderately differentiated histology, and pathological stages I and II. The radical resection rate of GC was significantly lower in synchronous patients than in metachronous patients (45.94% vs. 100.00%, P < 0.001), but no significant difference was noted in the radical resection rate of SPCs (35.13% vs. 46.34%, P = 0.315). The OS of DPCFGC patients was 31.03 ± 4.14 months. The pathological stage of GC and SPCs, whether to operate for GC, and diagnostic interval were independent risk factors. The predictive efficacy of the prognostic nomogram for 1-, 2- and 3-year OS in DPCFGC patients was 0.922, 0.935 and 0.796 , respectively, with good consistency and clinical applicability. The OS was significantly lower in the high-risk group than in the low-risk group. During follow-up, clinicians should attach great importance to the screening of GC survivors, especially at early stage in older men within 1 year after diagnosis, and be alert to the possibility of occurrent digestive system malignancies. The nomogram constructed in this study can provide a theoretical basis for the early clinical development of individualized treatment plans.

Abstract LB129: Survival of most commonly diagnosed second primary cancers among adult cancer survivors

Abstract Background Second primary cancer (SPC) burden is increasing in the US, but few studies comprehensively examined survival in persons diagnosed with SPCs in relation to survivors’ antecedent cancer types. Methods Persons aged ≥20 years and diagnosed with one of the six most common SPCs (female breast, prostate, bladder, lung, colorectum, corpus uteri) from 2000-2013 were identified from 17 Surveillance, Epidemiology, and End Results registries (n=152,204). For comparison, persons diagnosed with same type cancers occurring as first primary cancers (FPCs) were also identified (n=2,131,953). For each cancer type, differences in the risk of cancer-specific or all-cause death between SPC and FPC were estimated using multivariable Cox proportional hazards models adjusted for potential confounders. Subgroup analyses were conducted to estimate the risk difference between SPC and FPC by antecedent cancer types of those with SPCs. Results During a median follow-up of 6.5 years (interquartile range, 1.8-10.6), cancer-type specific death occurred among 34% of persons with SPCs and among 32% of persons with FPCs. The corresponding proportions for all-cause death were 67% and 53%, respectively. In multivariable models, the risk of cancer-specific death was statistically significantly higher in persons with SPC than in persons with FPC for breast (hazard ratio [HR]=1.43; 95% confidence interval [CI]=1.40-1.48), bladder (HR=1.19; 1.09-1.29), corpus uteri (HR=1.10; 1.05-1.15), and colorectal (HR=1.05, 1.03-1.07) cancer, whereas it was lower for lung cancer (HR=0.78; 0.77-0.79). The risk did not vary between groups for prostate cancer (HR=0.92; 0.79-1.06). Subgroup analyses showed large variations in HRs across survivors by antecedent cancer types. In particular, the highest HR associated with SPC (vs FPC) was among ovarian cancer survivors for colorectal cancer (HR=1.31; 1.10-1.56), gallbladder cancer survivors for breast cancer (HR=1.78; 1.09-2.91), head and neck cancer survivors for uterine cancer (HR=1.69, 1.05-2.72), gallbladder cancer survivors for bladder cancer (HR=1.87; 1.06-3.22), while the lowest HR for lung cancer was among testicular cancer survivors (HR=0.54; 0.38-0.76). Associations were generally consistent across strata of diagnosis years, race/ethnicity, household income, and urbanicity. The risks of all-cause death were also higher among persons with SPC vs FPC, including prostate cancer. Persons with second primary prostate cancer were almost twice as likely to die from all causes as persons with first prostate cancer (HR=1.83; 1.80-1.87). Conclusion Persons with SPC generally have a higher risk of cancer-specific and all-cause death than those with FPC, suggesting that intensive SPC surveillance may benefit those at increased risk of developing SPC. Importantly, the risk difference substantially varied by survivors’ antecedent cancer type, highlighting a need for targeted strategies for treatment and survivorship care for persons with SPCs. Citation Format: Hyuna Sung, Lauren Nisotel, Ephrem Sedeta, Farhad Islami, Ahmedin Jemal. Survival of most commonly diagnosed second primary cancers among adult cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB129.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Advances in radiotherapy and its impact on second primary cancer risk: A multi-center cohort study in prostate cancer patients

BackgroundModelling studies suggest that advanced intensity-modulated radiotherapy may increase second primary cancer (SPC) risks, due to increased radiation exposure of tissues located outside the treatment fields. In the current study we investigated the association between SPC risks and characteristics of applied external beam radiotherapy (EBRT) protocols for localized prostate cancer (PCa). MethodsWe collected EBRT protocol characteristics (2000–2016) from five Dutch RT institutes for the 3D-CRT and advanced EBRT era (N = 7908). From the Netherlands Cancer Registry we obtained patient/tumour characteristics, SPC data, and survival information. Standardized incidence ratios (SIR) were calculated for pelvis and non-pelvis SPC. Nationwide SIRs were calculated as a reference, using calendar period as a proxy to label 3D-CRT/advanced EBRT. ResultsFrom 2000-2006, 3D-CRT with 68–78 Gy in 2 Gy fractions, delivered with 10–23 MV and weekly portal imaging was the most dominant protocol. By the year 2010 all institutes routinely used advanced EBRT (IMRT, VMAT, tomotherapy), mainly delivering 78 Gy in 2 Gy fractions, using various kV/MV imaging protocols. Sixteen percent (N = 1268) developed ≥ 1 SPC. SIRs for pelvis and non-pelvis SPC (all institutes, advanced EBRT vs 3D-CRT) were 1.17 (1.00–1.36) vs 1.39 (1.21–1.59), and 1.01 (0.89–1.07) vs 1.03 (0.94–1.13), respectively. Nationwide non-pelvis SIR was 1.07 (1.01–1.13) vs 1.02 (0.98–1.07). Other RT protocol characteristics did not correlate with SPC endpoints. ConclusionNone of the studied RT characteristics of advanced EBRT was associated with increased out-of-field SPC risks. With constantly evolving EBRT protocols, evaluation of associated SPC risks remains important.

Second Primary Cancers in a Population-Based Mesothelioma Registry.

The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration. We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan-Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death. The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4-11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03). The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma.

Ten-Year Follow-up Results of Pure Ground-Glass Opacity–Featured Lung Adenocarcinomas After Surgery

Previously, we have demonstrated that the 5-year recurrence-free survival after surgery of pure ground-glass opacity (GGO)-featured lung adenocarcinoma is 100%. This study aimed to reveal the long-term outcomes of these patients 10 years after surgery. Lung adenocarcinoma patients who underwent surgery between December 2007 and December 2013 were reviewed. Patients with pure GGO-featured lung adenocarcinoma were enrolled. Postoperative survival and the risk of developing second primary lung cancer were analyzed. Overall, 308 cases of pure GGO-featured lung adenocarcinomas were included. Of these patients, 226 (73.4%) were female, 268 (87.0%) were nonsmokers, and 187 (60.7%) underwent sublobar resection. The median follow-up period after surgery was 112 months. The 10-year recurrence-free survival rate of these patients was 100%, and 10-year overall survival rate was 96.9%. Both 5-year and 10-year lung cancer-specific survival were 100%. There was no difference in 10-year recurrence-free survival rates between patients who underwent lobectomy or sublobar resection (P= .697). EGFR mutations were detected in 55.6% (84 of 151) of patients who underwent mutational analysis. The risk of developing secondary primary lung cancer for pure GGO-featured lung adenocarcinoma patients at 10 years after resection was 2.4%, and was not correlated with EGFR mutation status (P= .452). No recurrence was observed in patients with pure GGO-featured lung adenocarcinomas 10 years after surgery, even when pathologically evaluated as invasive adenocarcinoma. Pure GGO can be cured by surgery. Surgery is recommended for the appropriate time window with the view to cure. Our study emphasizes that radiologic pure GGO-featured lung adenocarcinomas should be distinguished from other lung adenocarcinomas.

Suicide rates among patients with first and second primary cancer.

With advancements in cancer treatments, the survival rates of patients with their first primary cancer (FPC) have increased, resulting in a rise in the number of patients with second primary cancer (SPC). However, there has been no assessment on the incidence of suicide among patients with SPC. This study assessed the occurrence of suicide among patients with SPC and compared them with that in patients with FPC. This was a retrospective, population-based cohort study that followed patients with FPC and SPC diagnosed from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 17 registries database between 1 January 2000 and 31 December 2019. For patients with SPC, an age of 85+years at diagnosis was associated with a higher incidence of suicide death (HR, 1.727; 95% CI, 1.075-2.774), while the suicide death was not considerably different in the chemotherapy group (P>0.05). Female genital system cancers (HR, 3.042; 95% CI, 1.819-6.361) accounted for the highest suicide death among patients with SPC. The suicide death distribution of patients with SPC over time indicated that suicide events mainly occurred within 5 to 15years of diagnosis. Compared with patients with FPC, patients with SPC in general had a lower risk of suicide, but increased year by year. The risk of suicide was reduced in patients with SPC compared with patients with FPC, but increased year by year. Therefore, oncologists and related health professionals need to provide continuous psychological support to reduce the incidence of suicide. The highest suicide death was found among patients with female genital system cancer.

The Incidence, Survival, and HPV Impact of Second Primary Cancer following Primary Oropharyngeal Squamous Cell Carcinoma: A 20-Year Retrospective and Population-Based Study.

Second primary cancer (SPC) is the second most common cause of death among patients diagnosed with head and neck cancer. This study examined the risk of SPC following oropharyngeal squamous cell carcinoma (OPSCC) and the impact of human papillomavirus (HPV) on survival following SPC. The study was a population-based, retrospective study including all patients diagnosed with OPSCC in eastern Denmark from 2000-2020 who received curative intended treatment. The incidence rate ratio (IRR), age-adjusted incidence rates (AAIR), and hazard ratios (HR) were calculated. A total of 2584 patients with primary OPSCC were included (median follow-up time: 3.1 years), with 317 patients (12.3%) diagnosed with SPC. The risk of SPC was approximately five times the occurrence of cancer in the general population (IRR: 4.96). The median time to SPC after a primary OPSCC was 2.0 years (interquartile range (IQR) = 0.6-4.2 years). HPV-positive (HPV+) patients had a significantly longer median time to SPC, and a significant better survival compared to HPV-negative (HPV-) patients. SPC was most frequently found in lungs, head, and neck (LHN) for HPV- OPSCC patients and lungs followed by gender-specific (prostate, ovaries, or endometrium) for HPV+ OPSCC. There was a significant difference between the two groups when distributed between "within" or "outside" LHN. Patients with SPC outside LHN had a significant better overall survival. This knowledge should be considered during post-treatment surveillance and might guide targeted imaging.

Racial and ethnic disparities in mortality among breast cancer survivors after a second malignancy.

Racial and ethnic differences in survival after a first cancer are well established but have not been examined after a second primary cancer (SPC) despite the increasing incidence among survivors. We examined 39 029 female breast cancer survivors who developed an SPC between 2000 and 2014 in the Surveillance, Epidemiology, and End Results 18 database. Multivariable Cox proportional hazards regression for competing risks data was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for cancer and cardiovascular disease mortality after SPCs comparing Hispanic, Non-Hispanic Asian, and Non-Hispanic Black survivors with Non-Hispanic White survivors. Models were adjusted for sociodemographics, tumor characteristics, and treatments of the first and second cancer. Analyses were stratified by SPC type. During 17 years of follow-up, there were 15 117 deaths after SPCs. The risk of cancer death was 12% higher among Non-Hispanic Black survivors (HR = 1.12, 95% CI = 1.05 to 1.19) and 8% higher among Hispanic survivors (HR = 1.08, 95% CI = 1.00 to 1.16) compared with Non-Hispanic White survivors. In subgroup analyses, the strongest associations were observed among Non-Hispanic Black survivors with a second breast or uterine cancer and among Hispanic survivors with a second breast cancer. Non-Hispanic Black survivors also experienced a 44% higher risk of cardiovascular disease death after SPC diagnosis than Non-Hispanic White survivors (HR = 1.44, 95% CI = 1.20 to 1.74). Higher cancer mortality among Non-Hispanic Black and Hispanic survivors and higher cardiovascular mortality among Non-Hispanic Black survivors exist among women who survive a first breast cancer to develop an SPC. Studies focused on identifying the contributors to these disparities are needed to enable implementation of effective mitigation strategies.

Secondary Primary Cancer after Primary Gastric Cancer: Literature Review and Big Data Analysis Using the Health Insurance Review and Assessment Service (HIRA) Database of Republic of Korea.

Advances in cancer screening and early detection, as well as improvements in surgical techniques and therapeutics, have contributed to decreasing gastric cancer mortality. The number of gastric cancer survivors continues to rise; however, long-term follow-up has revealed an increase in the risk of post-gastrectomy symptoms or other health problems, such as extra-gastric secondary primary cancer (SPC), in these survivors. Therefore, evidence-based screening for new primary cancer is needed in these populations; however, the incidence of SPC varies by country or continent and its characteristics have not been clearly reported. The characteristics of SPC are of increasing interest to both treatment providers and gastric cancer survivors; thus, this literature review explores not only the epidemiology and biology of SPC but also clinical and biological factors that influence its prognosis.

Incidence of second primary cancers in oral and pharyngeal cancer patients using a large medical claims database in Japan

Background/purposeAs the occurrence of second primary cancers (SPCs) is strongly related to the survival rate of patients with oral and pharyngeal cancers, early detection and treatment are important. Therefore, this study aimed to clarify the incidence of SPCs and their risk factors in patients with oral and pharyngeal cancer. Materials and methodsThis observational study was conducted using data from the administrative claims database of 21,736 participants with oral and pharyngeal cancer from January 2005 to December 2020. We evaluated the cumulative incidence of SPCs among patients with oral and pharyngeal cancers using the Kaplan–Meier method. The Cox proportional-hazard model was used for multivariate analysis. ResultsOf the 1633 patients with oral and pharyngeal cancer who qualified for analysis, 388 developed SPCs (incidence rate, 7.994/1000 person-months). The multivariate analysis showed that the risk of developing SPCs was affected by age at diagnosis of oral and pharyngeal cancer, cancer treatment, and anatomical site of the primary cancer. ConclusionPatients with oral and pharyngeal cancers are at a high risk of developing SPCs. The data from this study may be useful in providing accurate information to patients with oral and oropharyngeal cancer.

Incidence of second primary cancers among survivors of childhood cancer: A population-based study, Osaka, Japan, 1975-2015.

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR=28.0) followed by digestive system (EAR=15.1), thyroid (EAR=8.3), and bones and joints (EAR=7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

High incidence combination of multiple primary malignant tumors of the digestive system.

Clinical reports of multiple primary malignant tumors (MPMTs) in the digestive system are increasing. In China, although the survival rate of patients with MPMTs is increasing, the quality of life is very low. Many patients have reached the advanced stage when the second primary tumor is found, resulting in no early intervention and treatment. This is due to the misunderstanding of MPMTs by clinicians, who treat such tumors as metastases. Therefore, before a patient has a second primary tumor, doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient. To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization. A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively. They were divided into metachronous MPMT and synchronous MPMT groups, and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted. Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test, respectively. A P value < 0.05 was considered as statistically significant, and SPSS version 26.0 (SPSS Inc., Chicago, Illinois, United States) was used for statistical analysis. Among the 1902 patients with MPMTs confirmed by pathology, 1811 (95.2%) cases were secondary primary cancers, 89 (4.7%) cases were tertiary primary cancers, and 2 (0.1%) cases were quaternary primary cancers. Most (88.2%) of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer. The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows: Breast cancer, thyroid cancer, nonuterine cancer, lung cancer, colon cancer, kidney cancer, uterine cancer, bladder cancer, rectal cancer, and gastric cancer. The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer (11.6%), the highest incidence rate of the second primary cancer was still lung cancer (24.9%), the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer (32.7%), and the highest incidence rate of the second primary cancer was lung cancer (20.8%). Among them, breast cancer, nonuterine cancer and uterine cancer were female-specific malignant tumor types, and thyroid cancer also accounted for 79.6% of female patients. The top five metachronous cancer combinations, independent of female-specific malignant tumor types and thyroid cancer, were colon cancer and lung cancer (26 cases), kidney cancer and lung cancer (25 cases), rectal cancer and lung cancer (20 cases), gastric cancer and lung cancer (17 cases), and bladder cancer and lung cancer (17 cases). The most common synchronous cancer combination was colon cancer and rectal cancer (15 cases). Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Clinical and sociodemographic risk factors associated with the development of second primary cancers among postmenopausal breast cancer survivors.

Advancement in breast cancer (BC) diagnosis and treatment have increased the number of long-term survivors. Consequently, primary BC survivors are at a greater risk of developing second primary cancers (SPCs). The risk factors for SPCs among BC survivors including sociodemographic characteristics, cancer treatment, comorbidities, and concurrent medications have not been comprehensively examined. The purpose of this study is to assess the incidence and clinicopathologic factors associated with risk of SPCs in BC survivors. We analyzed 171, 311 women with early-stage primary BC diagnosed between January 2000 and December 2015 from the Medicare-linked Surveillance Epidemiology and End Results (SEER-Medicare) database. SPC was defined as any diagnosis of malignancy occurring within the study period and at least 6 months after primary BC diagnosis. Univariate analyses compared baseline characteristics between those who developed a SPC and those who did not. We evaluated the cause-specific hazard of developing a SPC in the presence of death as a competing risk. Of the study cohort, 21,510 (13%) of BC survivors developed a SPC and BC was the most common SPC type (28%). The median time to SPC was 44months. Women who were white, older, and with fewer comorbidities were more likely to develop a SPC. While statins [hazard ratio (HR) 1.066 (1.023-1.110)] and anti-hypertensives [HR 1.569 (1.512-1.627)] increased the hazard of developing a SPC, aromatase inhibitor therapy [HR 0.620 (0.573-0.671)] and bisphosphonates [HR 0.905 (0.857-0.956)] were associated with a decreased hazard of developing any SPC, including non-breast SPCs. Our study shows that specific clinical factors including type of cancer treatment, medications, and comorbidities are associated with increased risk of developing SPCs among older BC survivors. These results can increase patient and clinician awareness, target cancer screening among BC survivors, as well as developing risk-adapted management strategies.

36 (PB-036) Poster - Second primary cancer risks for female and male breast cancer survivors in England

Background: Second primary cancer (SPC) incidence is significantly increased following breast cancer (BC) diagnosis, but the magnitudes of these risks remain unclear. We estimated SPC risks following BC separately for males and females based on comprehensive data from linkage of National Cancer Registration and Analysis (NCRAS) and Hospital Episode Statistics (HES) electronic health records in England.