Relative survival among cancer survivors enrolled in private cancer insurance in Japan, using the internal insurance-enrolled population as the reference.

Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study

Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers. We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4months for the first 3years and every 6months thereafter. Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC. CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone.

819 Background: Incidence rates of rare appendiceal cancers are increasing across the United States. Although this is suggestive of a growing population of appendiceal cancer survivors over time, the risk of second primary cancers specific to patients with a first primary appendiceal adenocarcinoma remains unknown. Methods: We conducted a population-based study of adults (age ≥18 years) diagnosed with a first primary appendiceal adenocarcinoma from 1992 to 2021, using data from the Surveillance, Epidemiology, and End Results (SEER) Program. We estimated cumulative incidence of second primary cancer, defined as any primary cancer diagnosed at least 3 months after appendiceal adenocarcinoma, with Fine and Gray methods to account for the competing risk of death. For comparison to the general population, we also estimated standardized incidence ratios [SIRs], or the observed number of second cancers relative to the expected number based on age-, sex-, and race-specific incidence rates. Results: A total of 5,827 adults diagnosed with a first primary appendiceal adenocarcinoma (mean age 58.0 years; 51.8% female; 68.5% non-Hispanic White) were identified during the study period, of whom 418 developed a second primary cancer. The most common types of second primary cancer were prostate (17.7%), colorectal (14.4%), female breast (10.5%), lung (8.4%), and melanoma (6.0%). At 10 and 20 years after appendiceal adenocarcinoma diagnosis, the cumulative incidence of second primary cancer was 7.5% (95%CI 6.8%-8.4%) and 11.7% (95%CI 10.5%-12.9%), respectively. Cumulative incidence significantly differed by sex (p<0.01) and age at appendiceal adenocarcinoma diagnosis (early-onset [age<50] vs late-onset; p<0.01). For example, at 10 years post-diagnosis, the cumulative incidence of second primary cancer was 6.4% (95%CI 5.4%-7.4%) for females and 8.8% (95%CI 7.6%-10.1%) for males. The overall SIR for any second primary cancer was 1.12 (95%CI, 1.02-1.23)—corresponding to 14.8 excess cancers per 10,000 person-years. SIRs for common types of second primary cancers were: 1.07 (95%CI 0.84-1.35) for prostate, 2.12 (95%CI 1.63-2.70) for colorectal, 0.91 (95%CI 0.68-1.19) for female breast, 0.81 (95%CI 0.58-1.09) for lung, and 1.20 (95%CI 0.79-1.73) for melanoma. Conclusions: Approximately one in every 13 adults diagnosed with a first primary appendiceal adenocarcinoma in the United States will be diagnosed with a second primary cancer within 10 years. After diagnosis of an appendiceal adenocarcinoma, patients have a 12% excess incidence in second primary cancers and double the excess incidence in second primary colorectal cancers compared to the general population. Implementation of cancer prevention and early detection strategies (e.g., colonoscopy screening, genetic testing) for patients with an appendiceal adenocarcinoma is a clinical priority.

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

Objective To study the expression of MLH1 and PMS2 proteins and the characteristics of clinicopathological features. Methods A total of 205 071 patients with colorectal cancer data from 7 hospitals including the Chinese Academy of Medical Sciences Cancer Hospital from January 2010 to December 2018 were included in the study. 26 280 immunohistochemical information and case information met the research criteria. The relationship between MLH1 and PMS2 gene protein expression and age, sex, tumor size, pathological stage and other factors were analyzed. Results The MLH1 deletion rate was 4%, and the PMS2 deletion rate was 3.25%. There was a statistically significant difference in the ratio of male to female in the two patients with loss of protein expression (both P<0.001), and the age of onset was smaller than that in the normal expression group (both P<0.001). The incidence of the second primary cancer was also higher than that of the normal expression group (both P<0.001). The maximal tumor diameter of patients with MLH1 and PMS2 protein expression was greater than that of the normal expression group (all P<0.001), and the total number of lymph nodes cleared was also higher than the normal expression group (both P<0.001). In addition, the MLH1 expression-deficient group showed a clear tendency to familial aggregation compared to the normal group (P=0.001). At the site, the incidence of MLH1 and PMS2 protein deletions in the right colon was higher than in the normal expression group. In terms of tumor stage, the T stage of MLH1 and PMS2 protein was significantly different between the expression loss group and the normal group (P<0.001). In the M stage, the distant metastasis rate of patients with PMS2 protein deletion was lower than that of the normal group (P<0.001). Conclusion Patients with loss of MLH1 and PMS2 expression have earlier onset age, larger tumor volume, higher proportion of right colon, higher incidence of second primary cancer, higher number of lymph node dissection, and pathological staging. There is a close correlation. Key words: Colorectal neoplasms; Mismatch repair gene; MLH1; PMS2; Multicenter study; Big data platform

As the number of long-term cervical cancer survivors continues to increase because of improvements in treatment, concerns about second primary malignancy have grown. The high-risk area of second primary cancers in cervical cancer survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful marker for gynecological cancers. Thus, we designed a large-scale, nationwide, controlled cohort study to investigate whether PID or other risk factors increased the risk of second primary cancers in patients with cervical cancer treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer patients were identified using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan. Patients who received definite surgery were selected. To exclude the effect on second primary malignancy by treatment modalities, all cervical patients who ever having received adjuvant or definite radiotherapy or chemotherapy for primary cervical cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery alone without adjuvant treatments were analyzed.Cox proportional hazards model was used for multivariate analysis and the Kaplan–Meier method was used to assess the cumulative risks. Regarding the incidence of second primary cancers, the standardized incidence ratio (SIR) was used.The median follow-up time was 56.6 months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12% for PID and without PID, respectively. After adjustment for confounders, age of less than 50 years, the presence of diabetes mellitus, and PID were significantly positivity associated with the risk of second primary cancers. The hazard ratios (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI = 1.11–2.04), 1.40 (95% CI = 1.06–1.85), and 1.35 (95% CI = 1.00–1.81), respectively. A higher incidence of second primary cancers was observed in the genitals, bladder, and colon.In conclusion, the incidence of second primary cancers was higher in the genitals, bladder, and colon in patients with cervical cancer treated with surgery alone. The patients with PID had a higher risk of second primary cancers.

We aimed to investigate socio‐economic inequalities in second primary cancer (SPC) incidence among breast cancer survivors. Using Data from cancer registries in England, we included all women diagnosed with a first primary breast cancer (PBC) between 2000 and 2018 and aged between 18 and 99 years and followed them up from 6 months after the PBC diagnosis until a SPC event, death, or right censoring, whichever came first. We used flexible parametric survival models adjusting for age and year of PBC diagnosis, ethnicity, PBC tumour stage, comorbidity, and PBC treatments to model the cause‐specific hazards of SPC incidence and death according to income deprivation, and then estimated standardised cumulative incidences of SPC by deprivation, taking death as the competing event. Multiple imputation was performed to account for missing data. Among 649,905 included women, 47,399 SPCs and 171,223 deaths occurred during 4,269,042 person‐years of follow‐up. Income deprivation was consistently associated with an increased rate of SPC incidence (cause‐specific hazard ratio for the most vs. least deprived quintile: 1.29; 95% CI: 1.25, 1.33) and of death (1.36; 1.34, 1.38), translating into an absolute risk difference (the most vs. least deprived quintile) of 1.3% (95% CI: 1.0, 1.5) for SPC incidence and 4.9% (95% CI: 4.6, 5.1) for death at 10 years. Women with PBC from deprived areas in England faced a substantially higher risk of SPC than their counterparts. Future research is warranted to understand mechanisms for observed inequalities to inform strategies to monitor, prevent, and identify SPC in women with PBC.

Longitudinal studies are needed to characterise the burden of second primary malignancies among cancer survivors. Therefore, we quantified the incidence rate and cumulative incidence of second primary cancers (SPC) and standardised incidence ratios (SIR) in a population-based cohort of subjects diagnosed with a first primary cancer (FPC). We evaluated a cohort of cancer patients from the Portuguese North Region Cancer Registry (RORENO), with the first diagnosis in 2000-2003 (n = 39451), to estimate the incidence rate and cumulative incidence of SPC and standardised incidence ratios (SIR), for different periods of follow-up, up to 5 years; SPC were defined according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. The incidence rate of SPC was more than 5-fold higher in the first 2 months of follow-up than in the period between 2 months and 5 years (metachronous SPC), across which the incidence rates were relatively stable. Cancer survivors had an overall higher incidence rate of cancer than the general population (SIR = 1.31 (95 % confidence interval (CI), 1.25-1.38)), although that difference faded when only metachronous SPC were considered (SIR = 1.02 (95 % CI, 0.96-1.08)). Cancer incidence rates were higher among female lung FPC survivors and lower in prostate FPC cancer survivors than in the general population. The 5-year cumulative risk of developing a metachronous SPC was 3.0 % and reached nearly 5.0 % among patients with FPC associated with lower risk of death. Cancer survivors had higher incident rates of cancer that the general population, especially due to diagnoses in the first months following the FPC. Nevertheless, after this period SPC remain frequent events among cancer survivors. SPC constitute an important dimension of the burden of cancer survivorship, and this needs to be taken into account when defining strategies for surveillance, prevention and counselling.

e12054 Background: Late sequelae of breast cancer therapies potentially impact morbidity and mortality with increasing numbers of survivors. Radiation exposure has been linked to increased incidence of second primary cancers (SPC). However, to date, there is limited literature describing incidence of head and neck (HN) and esophageal cancers in patients with an index breast cancer (BC). This study aimed to describe the incidence of esophageal and HN cancers following breast cancer diagnosis. Methods: Standardized incidence ratios (SIRs) were calculated using the Surveillance, Epidemiology, and End Results (SEER) 9 database for BC patients diagnosed from 1973-2013. SIRs compared incidence of HN and esophageal cancer after an initial BC diagnosis to the general population. HN included oral cavity, pharynx, and larynx. BC patients were grouped into those who received radiotherapy for their breast cancer (n = 216,045) and those who did not (n = 289,596). SIRs were calculated in 5-year intervals. SEER does not contain information on chemotherapy. Results: Less than 1% of BC patients developed HN (0.3%) or esophageal cancers (0.1%), irrespective of radiation treatment. However, among patients with an index BC who received radiation therapy, there was significant but small increased incidence of HN and esophageal cancers five to nine years following treatment (HN SIR: 1.22; 95% CI, 1.04-1.43 and esophagus SIR: 1.44; 95% CI, 1.09-1.87). Esophageal cancer incidence continued to increase through 15 years of follow-up, however incidence of HN was not significant beyond ten years after the index BC diagnosis and radiation treatment. Conclusions: Compared to the general population, breast cancer patients have elevated incidence of HN and esophageal cancers detected five to nine years after receiving radiation treatment, but only the incidence of second primary esophageal cancer remains elevated at 15 years. These findings warrant further investigations of breast cancer radiation and future malignancies.

Increased survival and life expectancy among patients with prostate cancer results in an increased risk of developing a second primary cancer (SPC). We aimed to describe the occurrence of SPCs in a population-based cohort with a prostate first primary cancer (FPC), in Northern Portugal. A cohort of 13,222 patients with a prostate FPC from the North Region Cancer Registry of Portugal, diagnosed between 2000 and 2009, was followed until 31 December 2021, for synchronous (within six months of FPC diagnosis) and metachronous SPCs (all others). We describe absolute and relative frequencies of SPCs, incidence rates and standardized incidence ratios of SPCs (compared to the male general population), and cumulative incidence of metachronous SPCs. A total of 1953 (14.8%) patients with a prostate FPC developed an SPC, mostly of the colon, lung and bladder; synchronous SPCs occurred mainly in the bladder. Compared to the general male population, patients with a prostate FPC had a globally lower incidence of all cancers, and lung and oesophagus cancers, but a higher incidence of bladder and pancreas cancers. Overall, the incidence of synchronous SPCs was also significantly higher, likely reflecting the incidental diagnosis of SPCs. The 20-year cumulative incidence of metachronous SPCs was 15.4%. Patients with a prostate FPC had a lower overall incidence of SPCs than the general male population, despite a higher incidence in the first six-months after the SPC diagnosis. After that period, one out of seven may be expected to develop an SPC within two decades. Continued cancer surveillance among survivors is needed.

In a total of 2083 cases of hollow organ cancer of the head and neck region treated in our institute in the past 20 years, the relative risk of second primary cancers was statistically studied by the person-year approach. The organ association in multiple primary cancers and the relationship between tobacco and alcohol consumption and the development of second primary cancers were also reviewed. The incidence of second primary cancers was significantly (p < 0.05) higher in patients having a lesion at the tongue (n = 502), mesopharynx (n = 188), hypopharynx (n = 224) and larynx (n = 621) and in the oral cavity (n = 203) than in the general population. With regard to organ association in multiple primary cancers, cancers in the oral cavity, esophagus and at the pharynx were found to occur as second primary cancers of the tongue, oral cavity, meso-hypopharynx and larynx at significantly high rates in males. Male laryngeal cancer was related to the lung. No relation of female lingual cancer to the esophagus was noted. The incidence of second primary cancer was very high in persons who had been heavy smokers and/or heavy drinkers before the occurrence of their primary cancer in the head and neck region. In these people, second primary cancers were found to occur at high rates as cancers related to tobacco smoking and drinking. Otherwise, in cases with head and neck cancers less related to tobacco smoking and drinking, the incidence of second primary cancers was low. From the above results, tobacco smoking and drinking may be closely related to a high incidence of second primary cancer following the first primary cancer in the head and neck region.

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Solid organ transplanted patients have a three- to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model. We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years. During the follow-up, 499 subjects developed a first cancer (annual incidence: 98.6 x 10,000 PY), and 22 of them developed a SPC (annual incidence: 3.9 x 10,000 PY). The annual incidence of a SPC in the transplanted patients who developed a first cancer was 107.8 x 10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41). This result shows that the incidence of the SPC was the same as the incidence of a first cancer. Our study does not indicate an increased risk of SPC in transplanted subjects who already suffered a first malignancy.

74. GIST may have a higher incidence of second primary cancers which negatively impact upon survival

e15707 Background: Patients with primary colorectal cancer (CRC) are at an increased risk of developing a second primary cancer (SPC) at any site. In the United States, incidence patterns of primary CRC are shifting, with a notable rise in early-onset CRC and a decline in late-onset CRC. However, trends in SPC incidence remain poorly understood. We analyzed SPC incidence, stratified by the anatomical location and stage at diagnosis of primary CRC. Methods: CRC cases diagnosed between 2000-2018 were identified using SEER.Stat 8.4.4. Patients developing a SPC with a latency period of &gt; 6 months, and at a different location from the primary were identified. Incidence rates were calculated as the number of SPC cases in a given year divided by person-years at risk. Patients were categorized into four groups based on the location of primary CRC 1: cecum, ascending colon and hepatic flexure, 2: transverse colon, 3: splenic flexure, descending colon and sigmoid colon, and 4: rectosigmoid junction, and rectum. Stages at diagnosis of primary CRC were classified as early (in situ, localized) or late (regional, distant). Annual percentage change (APC) and average APC (AAPC) were estimated using Jointpoint regression and weighted Bayesian Information Criteria (P &lt; 0.05). Results: 40,022 (10.21%) patients developed a SPC over the study period. The overall incidence of SPC decreased from 2000 to 2009 (APC: -0.61 (-2.70,-0.10)), while it increased from 2009 to 2018 (APC: 0.58 (0.05,2.69)). For early-stage primaries, overall SPC incidence increased from 2009 to 2018 (APC: 0.90 (0.42,2.31)), following a period of stability from 2000 to 2009 (APC: -0.41%, (-1.95,0.03)). Among anatomical groups, early-stage rectosigmoid junction and rectum showed a consistent increase in SPC incidence from 2000 to 2018 (AAPC: 0.66 (0.06,1.26)). For late-stage primaries, a decline in incidence of SPC was observed from 2000 to 2010 (APC: -0.68(-3.39,-0.09)), followed by a stable trend from 2010 to 2018 (APC: 0.66 (-0.16,3.39)). Splenic flexure, descending colon and sigmoid colon demonstrated a notable decline from 2000 to 2004 (APC: -5.4 (-13.4,-0.80)), with a continued decline overall from 2000 to 2018 (AAPC: -0.79(1.15,-0.43)). Late-stage rectosigmoid junction and rectum showed a decrease in SPC incidence from 2000 to 2018 (AAPC: -0.79(-1.15,-0.43)). Conclusions: The incidence of second primary cancers following primary colorectal cancer demonstrates conflicting trends across different stages of diagnosis and anatomical sites. These trends are influenced by improved screening practices, shifting demographics, lifestyle modifications, and potential genetic predispositions. These findings highlight the importance of targeted surveillance and prevention strategies for specific anatomical sites and stages of CRC.