The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2.

PURPOSE: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies. METHODS: Exome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291). RESULTS: In total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T>C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins. CONCLUSION: Our study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.

The confusing pelvic mass: A case of small intestine lesion diagnosed by endoscopic ultrasound-guided fine-needle biopsy through the sigmoid colon.

Here we report a successful case of a small bowel lesion obtained through EUS-FNB via the sigmoid colon after routine small bowel endoscopy failed due to bowel volvulus. This case highlights the feasibility of EUS-FNB in small intestine lesion acquisition through sigmoid colon.

Research Progress of Multiple Primary Malignancies Associated With Esophageal Cancer.

With the improvement in survival of patients with tumors, and continuous advancement of diagnostic technology and treatment modalities, instances of multiple primary malignancies (MPMs) are becoming an increasingly common phenomenon. The occurrence of esophageal-relevant MPMs increases the difficulty of diagnosis and treatment, and the overall prognosis is poor. Esophageal cancer related-MPMs tend to occur in areas such as the head, neck, stomach, and lungs. "Field cancerization" is one theoretical basis for the disease, and chemoradiotherapy, environmental life factors, and gene polymorphism are etiological factors. However, the influence of new therapeutic methods on MPM is still unclear, and the relationship between gene polymorphism and MPMs related to esophageal cancer needs further elucidation. Additionally, there is a lack of unified standards for diagnosis and treatment. Therefore, this study aimed to review the causes, clinical features, and prognostic factors of MPMs related to esophageal cancer.

Differential treatment responses to immune checkpoint inhibitor (ICI) therapy in a case of multiple primary malignancies: the programmed death ligand-1 (PD-L1) negative ureteral and lung metastasis from a clear cell renal cell carcinoma appearing after robotic-assisted partial nephrectomy progressed after ICI therapy, while synchronous PD-L1-positive primary lung squamous cell carcinoma responded very well to ICI therapy: a case report.

BACKGROUND: Renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are representative malignancies that respond well to immune checkpoint inhibitors (ICIs). Research has been conducted to identify biomarkers, such as programmed death ligand-1 (PD-L1), that would allow the response to ICI therapy to be predicted; however, the complex tumor immune system consisting of both host and tumor factors may also exert an influence. CASE PRESENTATION: Computed tomographic imaging (CT) incidentally revealed a left renal mass, and a left pulmonary nodule with multiple lymph node metastases (LNMs). Firstly, video-assisted thoracic surgery revealed a lung tumor invading the chest wall. Histologically, the findings of the tumor were consistent with squamous cell carcinoma (SCC), and immunohistochemistry (IHC) showed positive PD-L1 expression. The renal tumor was excised by robotic-assisted partial nephrectomy (RAPN). Histologically, the renal tumor showed the features of clear cell carcinoma (CCC). Four months after the RAPN, CT revealed left hydronephrosis caused by an enhancing ureteral tumor. Then, multiple right lung metastases appeared, and the left lung tumor increased. Following treatment including atezolizumab, the primary lung SCC and the multiple LNMs almost disappeared completely, while the ureteral and right lung metastases showed progression. The ureteral metastasis was resected by left open nephroureterectomy. Histology of the ureteral tumor revealed features consistent with CCC. Histological examination of the multiple right lung metastases that were resected by partial lobectomy via a small thoracic incision also revealed features consistent with CCC. Two months after nephroureterectomy, a solitary left lung metastasis was treated by nivolumab and ipilimumab. Six months after nephroureterectomy, the patient died of RCC. Further studies of specimens revealed that the tumor cells in the primary RCC and the ureteral and lung metastases showed negative results of IHC for PD-L1. CONCLUSIONS: The responses to ICI therapy of concomitant RCC and NSCLC were quite different. The PD-L1 expression status in individual tumors in cases of multiple primary malignancies (MPMs) may directly predict the response of each malignancy to ICI therapy, because the host immune system, which may affect the response to ICI therapy, could be the same in MPMs.

Multiple Rare Primary Malignancies: A Mixed Squamous Neuroendocrine Adenocarcinoma of the Cervix, Metastasized Carcinosarcoma and Extramammary Vulvar Paget's Disease Case Report.

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget's disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget's disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team.

Multiple primary malignances managed with surgical excision: a case report with next generation sequencing analysis.

BACKGROUND: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases. METHODS AND RESULTS: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers. CONCLUSIONS: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development.

Survival of women diagnosed with breast cancer and who have survived a previous cancer.

PURPOSE: Many women diagnosed with breast cancer have survived previous cancer; yet little is known about the impact of previous cancer on overall and cancer-specific survival. METHODS: This population-based cohort study using SEER-Medicare data included women (age ≥ 66 years) diagnosed with breast cancer between 2005 and 2015. Separately by breast cancer stage, we estimated effect of previous cancer on overall survival using Cox regression and on cause-specific survival using competing risk regression; all survival analyses adjusted for covariates. RESULTS: Of 138,576 women diagnosed with breast cancer, 8% had a previous cancer of another organ site, most commonly colorectal or uterine cancer or melanoma. Many of these women (46.3%) were diagnosed within 5 years of breast cancer. For all breast cancer stages except IV wherein there was no difference, women with vs. without previous cancer had worse overall survival. This survival disadvantage was driven by deaths due to the previous cancer and other causes. In contrast, women with previous cancer generally had favorable breast-cancer-specific survival, although this varied by stage. Overall survival varied by previous cancer type, timing, and stage; previous lung cancer, cancer diagnosed within 1 year of incident breast cancer, and previous cancer at a distant stage were associated with the worst survival. In contrast, women with a previous melanoma had equivalent overall survival to women without previous cancer. CONCLUSION: We observed variable impact of previous cancer on overall and breast-cancer-specific survival depending on breast cancer stage at diagnosis and the type, timing, and stage of previous cancer.

Prognostic Impact and Clinicopathological Features of Multiple Colorectal Cancers and Extracolorectal Malignancies: A Nationwide Retrospective Study.

INTRODUCTION: Multiple primary malignancies (MPMs) are likely to develop in patients with colorectal cancer (CRC); however, their prognoses are unclear. This study aims to investigate the prognostic impacts and clinicopathological features of multiple CRCs and extracolorectal malignancies (EMs) with CRC. METHODS: We retrospectively evaluated a total of 22,628 patients with stage I-III CRC who underwent curative resection at 24 referral institutes in Japan between January 2004 and December 2012. MPMs were classified as synchronous CRCs (SCRCs), metachronous CRCs, synchronous EMs (SEMs), and metachronous EMs. RESULTS: The presence of SCRCs (odds ratio 1.54, p < 0.001) was independently associated with SEMs in the multivariate analyses. SEMs were the strongest poor prognostic factor for OS (hazard ratio [HR] 2.21, p < 0.001) and RFS (HR 1.69, p < 0.001) compared with age, sex, and primary T and N factors. The incidence of stomach cancer was the highest in EMs, followed by lung, breast, and prostate cancers. Multiple CRCs were evenly distributed throughout the right-side colon to the rectum. DISCUSSION/CONCLUSION: SEMs were a strong poor prognostic factor for patients with stage I-III CRC. Patients with CRC, particularly those with SCRCs, should be surveyed for SEMs, especially for stomach and lung cancers.

Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient.

Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.

Synchronous tumours detected during cancer patient staging: prevalence and patterns of occurrence in multidetector computed tomography.

PURPOSE: The incidental detection of one or more additional primary tumours during computed tomography (CT) staging of a patient with known malignancy is rare but possible. This occurrence should be considered by the radiologist when a new lesion is detected, especially if the lesion location is atypical for metastases. The purpose of this report was to document the usefulness of total body CT scan to detect synchronous primary malignancies in cancer patients undergoing a staging workup. MATERIAL AND METHODS: This was done by reviewing the staging CT studies of the adult patients with a newly diagnosed cancer evaluated during a five-year period in a single cancer institute in order to identify any possible correlation, establishing which tumours are more frequently combined with a second tumour and which second tumours are more commonly present. RESULTS: Among the patients with a second tumour, the most frequent first primary tumours were melanoma (eight patients, 17.8%), lymphoma (seven patients, 15.6%), and prostate carcinoma (seven patients, 15.6%). The most frequent incidentally detected second tumours were hepatocellular carcinoma (nine patients, 20% of 45 incidental tumours), renal carcinoma (eight patients, 17.8%), lung carcinoma (seven patients, 15.6%), and bladder carcinoma (four patients, 8.9%). One patient had three primary tumours synchronously. CONCLUSIONS: We believe that the radiologist's knowledge of the prevalence and pattern of occurrence of these multiple primary malignancies represents added diagnostic value.

Prognosis associated with synchronous or metachronous multiple primary malignancies in patients with completely resected non-small cell lung cancer.

PURPOSE: To investigate the influence of multiple primary malignancies (MPMs) on the prognosis of patients with completely resected non-small cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 521 patients who underwent complete curative pulmonary resection for NSCLC. Patients were divided into two groups: those with and those without MPMs. RESULTS: The 521 NSCLC patients included 184 patients (35.3%) with MPMs and 337 patients without MPMs. The overall 5-year survival rates for patients with vs those without MPMs were 66.1 and 75.6%, respectively (p = 0.0061). According to multivariate analysis, MPMs, age, gender, pathological stage, and interstitial pneumonia were independent predictors of prognosis. The 47 patients with synchronous MPMs and the 82 patients with metachronous MPMs found within the last 5 years had significantly poorer prognoses than patients without MPMs (p = 0.0048 and p = 0.0051, respectively). However, the prognoses of the 55 patients with metachronous MPMs that had been present for over 5 years did not differ from those of the patients without MPMs. CONCLUSIONS: NSCLC patients with synchronous MPMs or metachronous MPMs diagnosed within the last 5 years had poor prognoses. Decisions about the best therapeutic strategies require comprehensive consideration of the organ location, malignant potential, recurrence, and prognosis of the MPMs. In contrast, decisions about the best therapeutic strategies for NSCLC patients with metachronous MPMs present for over 5 years should be based solely on the NSCLC.

Current knowledge and future research directions in treatment-related second primary malignancies.

Currently, 17-19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk. In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer. Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose-volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening.

Multiple primary tumors in patients with surgically treated pancreatic cancer: a SEER population-based study.

Background: With improving survival after pancreatic cancer (PC) resection, questions emerge concerning risk and patterns of metachronous tumors. We aimed to determine the incidence of multiple primary cancers among postoperative PC survivors. Methods: Patients undergoing PC surgery from 1975 to 2020 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Standardized incidence ratios (SIRs) compared observed-to-expected cancers based on U.S. population rates. Cumulative incidence of secondary tumors was analyzed with Cox regression and cancer-specific survival with Kaplan-Meier curves. Results: Of 6,100 resected PC patients, 267 (4.38%) developed multiple cancers over 6.2 years median follow-up period. Subsequent malignancies showed a rising cumulative incidence extending beyond 5 years. Lung cancer was the predominant second primary in both males (n=36, SIR 1.87) and females (n=32, SIR 2.17). Prostate (n=33) and breast (n=25) cancers were also common. Risk varied by latency period and gender. Conclusions: Postoperative PC patients face a measurable risk for secondary cancers. Enhanced long-term surveillance has the potential to improve early detection and outcomes in this survivor population. Our data provides real-world evidence which could help inform surveillance guidelines in the future.

A rare occurrence of breast, thyroid, and stomach tumors in a single patient: A case report.

INTRODUCTION AND IMPORTANCE: There are only a few case reports to date that have described patients with three or more multiple primary tumors. However, they have been reported more in the last decade, so a precise screening in patients with or without risk factors could be helpful in early diagnosis and treatment. This work has been reported in line with the SCARE criteria. CASE PRESENTATION: Here, we presented a 44-year-old female patient without any history of smoking, alcohol consumption, or cancer in her family. She had three metachronous primary tumors; breast, thyroid, and gastric cancer, which had metastasized to both her ovaries and colon. She died in January 2023 due to complex pneumonia and septic shock. To our knowledge, this article is the second case in which breast, thyroid, and stomach cancer are reported together. CLINICAL DISCUSSION: When it comes to Multiple primary malignancies (MPMs), not only screening in patients with risk factors should be considered, but patients without any other risk factors except current or past history of tumors should be screened precisely for early diagnosis and treatment. In this study, we discuss prevalence and causes of MPMs, prevalence of breast, thyroid, and stomach cancer, and also their possible relations with each other that may affect their occurrence. CONCLUSION: Reporting other cases with MPMs by physicians could lead to establish an evidence based approach to these patients.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Synchronous Invasive Ductal Carcinoma of Breast and Diffuse Large B-cell Lymphoma: A Case Report.

Introduction: It is uncommon for breast cancer and non-Hodgkin lymphoma to present simultaneously. An increase in the rate of simultaneous malignancy identification has resulted from adopting more sensitive staging imaging techniques. Case Description: Here, we describe a patient who was diagnosed with axillary diffuse large B cell lymphoma (DLBCL) in a cancer hospital during a staging work-up for suspected breast cancer. Breast cancer was staged as Stage IIA and DLBCL as Stage IE. She was given three cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP) protocol. Interim positron emission tomography scan showed a complete metabolic response (Deauville score 2). She was given one more cycle of R-CHOP. Then, she had right breast-conserving surgery with axillary lymph node dissection in August 2023. Histopathology report showed residual disease with ductal carcinoma in situ. She was recommended weekly paclitaxel for 12 cycles and trastuzumab and pertuzumab for 1 year. She is currently having her adjuvant systemic therapy, after which she will be planned for local radiation. Endocrine treatment will be started once chemotherapy is completed. Practical Implications: Complete baseline work-up per standard protocols/guidelines should be done in each malignancy. Biopsy of metastatic sites should be done wherever possible. All histopathologies should be reviewed thoroughly before treatment initiation, as they may significantly alter patient management.

[Multiple primary malignancies combined with SWI/SNF complex-deficient gastric cancer: a case report and literature review].

Multiple primary malignancies combined with SWI/SNF complex-deficient gastric cancer is a rare clinical entity and poorly documented. Herein we report a case of this disease in an 81-year-old male patient treated in our hospital. Before the established diagnosis of metachronous multiple primary malignancies, the patient received left lower lobectomy for a spaceoccupying mass in the left lung, which was confirmed by postoperative pathology as early stage lung cancer. SWI/SNF complex-deficiency gastric cancer with metastasis was subsequently detected by gastroscopy, and high-throughput sequencing identified ARID1A and TMB-H gene mutations in the tumor tissues. The patient received chemotherapy combined with immunotherapy but failed to respond to the treatment, and died 13 months later. We conducted a literature review and analyzed the occurrence, pathological and immunohistochemical characteristics, diagnosis, treatment and prognosis of this disease.

Clinical and genetic characteristics in lymphoma patients with a second solid malignancy.

Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.

Risk and prediction of multiple primary malignancies after early gastric cancer.

Background: Patients with early gastric cancer have increased risk of developing multiple primary malignancies (MPM) due to improved survival rates. The purpose of this study was to evaluate the clinicopathological features of MPM and to generate a useful tool for predicting the development of MPM after early gastric cancer. Methods: We selected 1025 early gastric cancer patients with complete medical records for a retrospective analysis. The Cox proportional risk regression model was used to analyze the independent risk factors for the development of MPM in early gastric cancer. RStudio software was used to compare the OS of early gastric cancer patients with and without MPM, and a nomogram was established to predict the probability of MPM 1-, 2-, 3-year after early gastric cancer. The predictive effectiveness of the nomogram was evaluated by the C-index and calibration curve. Decision curve analysis (DCA) measured the applicability of the nomogram to clinical practice. Results: Of the 1025 patients with early gastric cancer, 66 patients (6.4%) had 69 primary cancers other than early gastric cancer. They had a median follow-up of 41 months, and their cumulative incidence of MPM was 4.9%, 5.4% and 5.9% after 1-, 2-, and 3- year, respectively. Oesophageal cancer was the most frequently detected MPM, followed by lung and colorectal cancers. Male (p=0.038), age ≥65 years (p=0.003), smoking history (p=0.036), and lymph node metastasis (p=0.013) were independent risk factors for MPM in patients with early gastric cancer. Patients with early gastric cancer with MPM had a worse OS prognosis than patients with early gastric cancer without MPM (p<0.001). The internally validated nomogram predicted the probability of developing MPM after early gastric cancer (C index= 0.697). The calibration chart showed that the predicted probability of MPM in early gastric cancer was similar to the observed result, and the DCA showed strong clinical practicability. Conclusion: After the diagnosis and treatment of early gastric cancer, we should be alert to the possibility of MPM and perform regular and careful monitoring.

Corrigendum: Risk and prediction of multiple primary malignancies after early gastric cancer.

[This corrects the article DOI: 10.3389/fonc.2023.1205358.].