Multiple Primary Cancers Research Articles

Synchronous lung cancer presenting with small cell carcinoma and squamous cell lung carcinoma: a case report.

Synchronous multiple primary lung cancers are separate tumors presenting at the same time with different histology. We present a rare case of a 64-year-old patient with a combination of small-cell lung carcinoma (SCLC) and squamous carcinoma in two different sites with metastasis of SCLC in the mediastinal lymph node. The SCLC diagnosis was performed via bronchoscopy, and the other diagnosis via CT-guided transthoracic biopsy. It is often difficult to distinguish a synchronous tumor from intrapulmonary metastases. To date, there are no guidelines for the treatment of these cases. The management of synchronous multiple primary lung cancer (SMPLC), mainly surgical with chemotherapy or radiotherapy, must be studied according to the histological type, staging and molecular testing of the tumors. These rare cases of SMPLC require individual treatment and a multidisciplinary approach.

Clinicopathological features and prognosis of synchronous and metachronous colorectal cancer: a retrospective cohort study.

To investigate the clinicopathological features and prognosis of synchronous and metachronous multiple primary colorectal cancer. Patients who underwent operation for synchronous and metachronous colorectal cancer at the colorectal surgery department of Shanghai Changhai Hospital between January 2000 and December 2021 were included. Perioperative indicators were comprehensively compared and included in the survival analyses. In total, 563 patients with synchronous ( n =372) and metachronous ( n =191) colorectal cancer were included. Patients with synchronous colorectal cancer were more likely to have a long onset time, positive carcinoembryonic antigen, advanced TNM stage, large tumor, perineural invasion, p53 high expression, and mismatch repair proficient. Compared with metachronous colorectal cancer, patients with synchronous colorectal cancer showed worse 5-year overall survival (68.6±3.0% vs 81.9±3.5%, P =0.018) and 5-year disease-free survival (61.2±3.1% vs 71.0±3.9%, P =0.022). In the subgroup analysis, segmental resection was an independent risk factor for the long-term outcomes of bilateral synchronous colorectal cancer. Clinicopathological and molecular features were different between synchronous and metachronous colorectal cancer. Patients with synchronous colorectal cancer showed a worse prognosis than those with metachronous colorectal cancer. Bilateral synchronous colorectal cancer requires extended resection to achieve improved long-term outcomes.

A prospective observational study to assess the epidemiological profile of multiple primary cancers in Eastern India.

Multiple primary cancers once thought to be rare have become increasingly common as the lifespan of cancer survivors has increased with availability of better and more effective cancer treatment. However, their exact incidence is not known and data on their epidemiological characteristics are not available. The aim of this study is to study the epidemiologic characteristics of multiple primary cancers in the eastern region of India. The study was conducted in the Department of Surgical Oncology, Medical College, Kolkata, from 2017 to 2020 over a period of 3 years. All patients with a diagnosis of second primary as per International Agency for Research on Cancer (IARC) definition or those developing a second primary within the study period were included for analysis. Data were recorded in form of preformed questionnaires. All the cases were followed up for at least 12 months. Fifty cases of multiple primary tumors were identified, out of which 21 were synchronous while rest 29 were metachronous type. The male-female ratio was 1:1.2. The median age at presentation for index malignancy was 50 years. The most common malignancy in the synchronous group was a combination of variety of GI cancers (six cases). In the metachronous category, a combination of reproductive cancers (breast, ovary, cervix, and endometrium) along with Gastrointestinal cancer (GI) cancers (colon, rectum) was most frequently found (eight cases). Definite risk factors for multiple primary tumors were identifiable in 10 cases: arsenic exposure in 5 cases, hereditary in 4 cases, and immunosuppression in 1, while in 8 cases, risk factors were only speculative (radiation 5 cases, chemotherapy 3). At the time of the last follow-up, 36 subjects were alive and 3 dead while the status of 11 subjects was unknown. This is the first comprehensive study on multiple primary cancers and the largest so far in India. Our study overcomes the shortcoming of previous case series from our subcontinent. The merits of our study include the use of the most accepted IARC definition, updated staging guidelines with long follow-up, and reliable survival data. Additionally, we could identify risk factors in 50% of our subjects. And our study shows various new combinations of cancers not reported before. Clustering of cases in the young adolescent group (25-49) years is also a new finding. We also highlight the existing ambiguity in the way this entity is defined. Demerits include the loss of follow-up data in a significant number of patients.

Successful delivery after in vitro fertilization-embryo transfer in a woman with metachronous primary cancer of ovary and endometrium: a case report

BackgroundThe appearance of malignancies at various times in the same individual, excluding metastases of the initial primary cancer, is termed multiple primary cancers. Double primary gynecological cancers cause inevitable damage to female reproductive function, and the preservation of fertility in such patients remains a challenging issue as relatively few cases have been reported. This case report provides management options for dual primary ovarian and endometrial cancers, including the choice of ovulation induction protocols, considerations during pregnancy and parturition, with the aim of providing assistance to clinicians.Case presentationWe report a case of a 39-year-old woman with primary infertility and a medical history of right-sided ovarian mucinous borderline tumor with intraepithelial carcinoma, left-sided ovarian mucinous cystadenoma and endometrial cancer, who successfully conceived with in vitro fertilization-embryo transfer (IVF-ET) after three different ovulation induction protocols. During her pregnancy, she was complicated by central placenta praevia with placental implantation and eventually delivered a healthy female infant by caesarean section at 33 gestational weeks.ConclusionsFor patients with double primary gynecological cancers who have an intense desire for fertility, the most appropriate oncological treatment should be applied according to the patient’s individual situation, and fertility preservation should be performed promptly. Ovulation induction protocol should be individualized and deliberate, with the aim of ensuring that the patient’s hormone levels do not precipitate a recurrence of the primary disease during induction of ovulation and maximizing fertility outcomes. In addition, the risk of postpartum hemorrhage due to placental factors cannot be neglected in such patients.

An unusual occurrence of synchronous invasive duct carcinoma and multiple myeloma – A case report

The cancer survival rates continue to increase with the passing day owing to advances in diagnostic modalities, therapeutic strategies and the ongoing research. Simultaneously, there is also an increase in the incidence of multiple primary cancers due to the increased survival, long term effects of chemotherapy and/or radiation therapy, higher diagnostic sensitivity and the persisting effects of behavioural and genetic risk factors. Multiple Primary Malignancies (MPM) was first described in 1879 by Billroth. Multiple primary tumours are defined as synchronous or metachronous tumours presenting in the same individual. The neoplasms may be limited to a single organ or may involve multiple anatomical organs. This article presents a case study of a 72-year old female, who was referred to our institute with a history of lump in the left breast and fracture of left clavicle.

Lineage tracing for multiple lung cancer by spatiotemporal heterogeneity using a multi-omics analysis method integrating genomic, transcriptomic, and immune-related features.

The distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) holds clinical significance in staging, therapeutic intervention, and prognosis assessment for multiple lung cancer. Lineage tracing by clinicopathologic features alone remains a clinical challenge; thus, we aimed to develop a multi-omics analysis method delineating spatiotemporal heterogeneity based on tumor genomic profiling. Between 2012 and 2022, 11 specimens were collected from two patients diagnosed with multiple lung cancer (LU1 and LU2) with synchronous/metachronous tumors. A novel multi-omics analysis method based on whole-exome sequencing, transcriptome sequencing (RNA-Seq), and tumor neoantigen prediction was developed to define the lineage. Traditional clinicopathologic reviews and an imaging-based algorithm were performed to verify the results. Seven tissue biopsies were collected from LU1. The multi-omics analysis method demonstrated that three synchronous tumors observed in 2018 (LU1B/C/D) had strong molecular heterogeneity, various RNA expression and immune microenvironment characteristics, and unique neoantigens. These results suggested that LU1B, LU1C, and LU1D were MPLC, consistent with traditional lineage tracing approaches. The high mutational landscape similarity score (75.1%), similar RNA expression features, and considerable shared neoantigens (n = 241) revealed the IPM relationship between LU1F and LU1G which were two samples detected simultaneously in 2021. Although the multi-omics analysis method aligned with the imaging-based algorithm, pathology and clinicopathologic approaches suggested MPLC owing to different histological types of LU1F/G. Moreover, controversial lineage or misclassification of LU2's synchronous/metachronous samples (LU2B/D and LU2C/E) traced by traditional approaches might be corrected by the multi-omics analysis method. Spatiotemporal heterogeneity profiled by the multi-omics analysis method suggested that LU2D possibly had the same lineage as LU2B (similarity score, 12.9%; shared neoantigens, n = 71); gefitinib treatment and EGFR, TP53, and RB1 mutations suggested the possibility that LU2E might result from histology transformation of LU2C despite the lack of LU2C biopsy and its histology. By contrast, histological interpretation was indeterminate for LU2D, and LU2E was defined as a primary or progression lesion of LU2C by histological, clinicopathologic, or imaging-based approaches. This novel multi-omics analysis method improves the accuracy of lineage tracing by tracking the spatiotemporal heterogeneity of serial samples. Further validation is required for its clinical application in accurate diagnosis, disease management, and improving prognosis.

Factors That Determine Multiple Primary Cancers in the Adult Population in the United States.

Cancer is a major public health problem worldwide and a leading cause of death in the United States. Multiple primary cancers mean that an individual has more than one cancer in the same or a different organ but does not include instances of metastasis of initial primary cancer. Several factors such as genetics, for example, BRCA1 gene mutations, may predict multiple primary cancers. Factors such as the age at first cancer diagnosis may determine the outcome of multiple primary cancers. This study aims to determine factors that determine multiple primary cancers among the adult population in the United States. Methods: This study uses data from the Behavioral Risk Factor Surveillance System 2021 dataset. The study included all individuals recently diagnosed with cancer (sample size = 9806). All age groups were included in this study. Measures included the outcome variable number of cancers and a major independent variable: age at first cancer diagnosis. Covariates included race, sex, smoking status, and cancer treatment. Descriptive, bivariate, and multivariate logistic regressions were conducted using a statistical analysis system. It was hypothesized that individuals with age at first diagnosis of cancer at a younger age have higher odds of having multiple primary cancers as compared to individuals diagnosed at an older age. Results:The age group of 50-64 years had the highest percentage of only one cancer type (35.87%) and of two or more cancers (35.46%). A majority of females had two or more cancers (53.52%) as compared to males (47.48%). The majority of participants with only one cancer type (80.59%) and two or more cancers (88.61%) were of White non-Hispanic ethnicity. At the multivariate level,the age group under 18 years had 9.4% higher odds of having two or more cancers compared to the age group of 18-29 years (adjusted OR (AOR)=1.094, 95%CI=1.026-1.166; p-value=0.0057). The age group 65 years and above had 11.6% lower odds of having multiple primary cancers as compared to the age group of 18-29 years (AOR=0.884; 95%CI=0.859-0910; p-value=<0.0001). The Black non-Hispanic group had 73.8% lower odds of having multiple primary cancers as compared to White non-Hispanic respondents (AOR= 0.262; 95%CI = 0.228-0.301; p-value = <0.0001).Hispanic respondents had 59.8% lower odds of having two or more cancers as compared to the White non-Hispanicgroup (AOR= 0.402; 95%CI=0.390-0.413; p-value=<0.0001). Current smokers had 9.7% higher odds of having multiple cancers as compared to individuals who never smoked (AOR = 1.097; 95%CI=1.066-1.129; p-value=<0.0001). Former smokers had 24.2% higher odds of having multiple cancers as compared to individuals who never smoked (AOR=1.242; 95%CI=1.224-1.261; p-value=<0.0001). Individuals who were currently on treatment had 2.676 higher odds of having two or more cancers as compared to individuals not on treatment (AOR=2.676; 95%CI=2.629-2.724; p-value=<0.0001). Conclusion: Multiple primary cancers have been on the increase recently following advancements in anticancer therapy and cancer screening and diagnosis technology. It is important that studies that aim to demonstrate risk factors and predictors of multiple primary cancers such as the age at first diagnosis, smoking status, and cancer treatment are encouraged among public health specialists.

Multiple Primary Cancer: Genetic Pathomorphological Factors of Endometrial and Breast Cancer

In this article, the results of detailed research on the genetic pathomorphological factors of multiple primary cancers: endometrial and breast cancer are presented. Also, the article provides detailed information about breast cancer, which ranks first in the world according to the index of female scientists, the causes of breast cancer, and the use of a new approach to treatment. Our new ideas and opinions about the treatment of patients with the combined use of radiotherapy and chemotherapy are presented.

Pathogenesis of selected multiple primary neoplasms

Introduction and aim. Multiple primary tumors are defined as having more than one primary tumor in a different organ location in the same person. Therefore, it is important to know pathogenesis of multiple primary neoplasms to discover new forms of primary prevention and secondary prevention, especially connected with genetic tests which are important for the future of medicine as a part of personalized medicine. The aim of the study is to present selected aspects of the pathogenesis of multiple primary neoplasms. Material and methods. PubMed databases and Google Scholar were searched. Analysis of the literature. The rising risk of developing multiple primary cancers is a consequence of the progressive growth and ageing of the population and development of cancer in patients previously treated for cancer. The formation of secondary neoplasms may be multifactorial – to a large extent it is associated with genetic factors that may facilitate neoplastic transformation, for example as a result of radiation therapy, chemotherapy, inherited syndromes, environmental factors such as tobacco or alcohol, sometimes random somatic mutations. Conclusion. Knowledge of the pathogenesis of multiple primary tumors can contribute to a better understanding of the problem, as well as help in the prevention or early diagnosis of multiple primary tumors (primary and secondary prevention).

Oncologic Outcomes of T1–T2N0 Glottic Cancer Treatment: Single Center Experiences of 417 Patients Over 20 Years

Background and Objectives For T1–T2 early glottic cancer, single modality treatment with radiation therapy (RT) or transoral laser microsurgery is the standard therapeutic option. However, the choice between surgery and RT has been debated for decades. Even though patient selection bias for each modality inherently exists in the retrospective study, this study aimed to compare the oncologic outcomes of the actual treatment of these patients between surgery-based treatment and RT.Materials and Method The medical records of 417 patients with T1–T2N0 glottic squamous cell carcinoma were reviewed who were treated at our institution between 1995 and 2014. The patients were divided into two groups; primarily surgery-based treatment (OP, n=209) or RT (n=208).Results In the T1 stage, local failure, overall survival (OS), and disease-free survival (DFS) rates were not different between the OP and RT groups. However, in the T2 stage, the local failure rate was higher in the RT group (p&lt;0.01). OS and DFS were higher in the OP group (p=0.019 and p=0.004, respectively). Larynx-preservation rate was similar in both groups (97.1% and 96.2%, p=0.576). Multivariate analysis showed that age (&gt;65), presence of multiple primary cancer, and treatment modality were significant variables influencing OS and DFS.Conclusion Surgery-based treatment provided better local control rates, DFS, and OS in patients with T1–T2N0 glottic SCC. In the T1 stage, treatment outcomes were similar between OP and RT groups. In the T2 stage, OP showed better results than RT, suggesting that refined strategies are required to improve the oncologic outcomes of RT for T2 glottic cancer.

A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report

BackgroundThe development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma.Case presentationA 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later.Conclusion18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.

A Case of Synchronous Rectal Cancer and Right Sided Colon Cancer Treated with Transvaginal NOSES Technique

Introduction: We reported a 53 years old female patient with synchronous rectal cancer and right sided colon cancer who underwent transvaginal NOSES to resect two tumors with no serious postoperative complications. Case report: The patient underwent electronic colonoscopy and found two lesions in the intestine, located in the right colon and rectum. Pathological examination confirmed that both lesions were malignant tumors, and the patient was diagnosed with concurrent colon and rectal cancer. After diagnosis, the patient underwent transvaginal NOSES, and the intraoperative exploration results were consistent with electronic colonoscopy. The surgery completely resected two malignant tumors at same time. The pathological report staging of right colon cancer is AJCC stage II (pT3N0M0), with moderately differentiated adenocarcinoma and negative circumferential margin. The pathological report staging of rectal ancer is AJCC stage IIIpT2N1aM0), with moderately differentiated adenocarcinoma and negative circumferential margin. The patient recovered well after surgery and did not experience any serious postoperative complications. Patient receives XELOX chemotherapy after surgery. Discussion: Transvaginal NOSES is a safe and effective surgical method for synchronous multiple primary colorectal cancer. However, due to the complexity of the surgery and the increased anesthesia risks associated with additional surgical time, experienced surgical and anesthesia teams are required. Conclusion: The application of transvaginal NOSES in the treatment of synchronous multiple primary colorectal cancer is still in the exploratory stage, and more clinical studies are needed to prove its feasibility, safety, and effectiveness.

Clinicopathological characteristics of synchronous multiple primary early esophageal cancer and risk factors for multiple lesions.

With the development of endoscopic technology, the detection rate of synchronous multiple primary early esophageal cancer (SMPEEC) is increasing; however, the risk factors remain unclear. We aimed to assess the clinicopathological characteristics of patients with SMPEEC and investigate the risk factors contributing to the development of multiple lesions. A retrospective cohort study was conducted on 911 consecutive patients who underwent Endoscopic submucosal dissection (ESD) for primary esophageal neoplasms from January 2013 to June 2021. The patients were divided into the SMPEEC group and the solitary early esophageal cancer (SEEC) group. We compared the differences in clinicopathological characteristics between the two groups and investigated the risk factors linked to multiple lesions. Additionally, we investigated the relationship between the main and accessory lesions. A total of 87 SMPEEC patients were included in this study, and the frequency of synchronous multiple lesions was 9.55% in patients with early esophageal cancer. The lesions in the SMPEEC group were mainly located in the lower segment of the esophagus (46[52.9%]), whereas those in the SEEC group were in the middle segment (412[50.0%]). The pathology type, tumor location, and circumferential rate of lesions were independent risk factors(P<0.05) for SMPEEC by logistic regression analysis. Significant positive correlations were observed between the main and accessory lesions in terms of morphologic type (r=0.632, P=0.000), tumor location(r=0.325, P=0.037), pathologic type (r=0.299, P=0.003), and depth of invasion (r=0.562, P=0.000). Pathology type, tumor location, and circumferential rate of lesions were identified as independent risk factors for SMEPPC. Understanding these risk factors and the correlation between the main and accessory lesions could significantly improve the detection rate of SMPEEC.

The place of multiple primary cancers in urologic oncology

Background. In Russia, statistical record of multiple primary cancers has been implemented only recently, and there are few scientific publications. Multiple primary malignant neoplasms of the urologic locations are described even less in literature. The problem of multiple tumors becomes more pressing with each passing year.Aim. To perform retrospective study of statistical data on urologic multiple primary cancer from one department.Materials and methods. An analysis of retrospective data from medical histories of patients who received treatment between 1997 and 2020 in urologic oncology departments where the authors worked: Omsk Regional Oncological Dispensary (1997–2005), Moscow Oncology Clinical Hospital No. 1 (2003–2005), Moscow City Oncology Hospital No. 62 was performed.Results. During the analyzed period, 23,299 hospitalizations including repeated were registered for 19,040 patients. Year-by-year data analysis showed 1,817 patients with multiple tumors, among them 1,508 patients with multiple primary malignant tumors, one and/or more of which were urologic pathology. The most common diseases were bladder cancer (n = 631), renal cancer (n = 618), prostate cancer (n = 614). A significant number of patients (n = 125; 8.29 %) had multiple tumors in 3 or more urologic locations. Tumors of the upper urinary tract were observed in 78 patients, testicle – in 36, penis – in 22, adrenal gland – in 10, urethra – in 4. Women comprised 28.05 % (n = 423) of the patients, men – almost 72 % (n = 1,085). This patient distribution by sex reflects the fact that urologic oncology includes both tumors of the urinary tract and male sex organs.Conclusion. Currently, the questions of terminology of multiple primary tumors remain open: multiple primary, multilocular, bilateral tumors, and mixed tumors. There is a lack of understanding in definition of the border between implantation metastases and multiple primary tumors in upper tract urothelial carcinoma and bladder cancer, between metastatic or bilateral tumors in bilateral renal cell carcinoma of the same morphology, etc.

Clinical Features of Li-Fraumeni Syndrome in Korea.

Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS. Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected. Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively. This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Developing prognostic nomograms to predict overall survival and cancer-specific survival in synchronous multiple primary colorectal cancer based on the SEER database.

Synchronous multiple primary colorectal cancer (SMPCC) is a rare subtype of CRC, characterized by the presence of two or more primary CRC lesions simultaneously or within 6months from the detection of the first lesion. We aim to develop a novel nomogram to predict OS and CSS for SMPCC patients using data from the SEER database. The clinical variables and survival data of SMPCC patients between 2004 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Appropriate inclusion and exclusion criteria were established to screen the enrolled patients. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors for OS and CSS. The performance of the nomogram was evaluated using the concordance index (C-index), calibration curves, and the area under the curve (AUC) of a receiver operating characteristics curve (ROC). A decision curve analysis (DCA) was generated to compare the net benefits of the nomogram with those of the TNM staging system. A total of 6772 SMPCC patients were enrolled in the study and randomly assigned to the training (n = 4670) and validation (n = 2002) cohorts. Multivariate Cox analysis confirmed that race, marital status, age, histology, tumor position, T stage, N stage, M stage, chemotherapy, and the number of dissected LNs were independent prognostic factors.The C-index values for OS and CSS prediction were 0.716 (95% CI 0.705-0.727) and 0.718 (95% CI 0.702-0.734) in the training cohort, and 0.760 (95% CI 0.747-0.773) and 0.749 (95% CI 0.728-0.769) in the validation cohort. The ROC and calibration curves indicated that the model had good stability and reliability. Decision curve analysis revealed that the nomograms provided a more significant clinical net benefit than the TNM staging system. We developed a novel nomogram for clinicians to predict OS and CSS, which could be used to optimize the treatment in SMPCC patients.

Racial and Ethnic Disparities in Survival Among People With Second Primary Cancer in the US

Comprehensive data for racial and ethnic disparities after second primary cancers (SPCs) are lacking despite the growing burden of SPCs. To quantify racial and ethnic disparities in survival among persons with SPCs. This population-based, retrospective cohort study used data from 18 Surveillance, Epidemiology, and End Results registries in the US for persons diagnosed with the most common SPCs at age 20 years or older from January 1, 2000, to December 31, 2013 (with follow-up through December 31, 2018). Data were analyzed between January and April 2023. Race and ethnicity (Hispanic, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, and non-Hispanic White). The main outcomes were 5-year relative survival and cause-specific survival. Cause-specific hazard ratios (HRs) were calculated for death from cancer or cardiovascular disease (CVD) in each racial and ethnic minority population compared with the White population overall and stratified by SPC type, with adjustment for sex, year and age at SPC diagnosis, and prior cancer type and stage (baseline model) and additionally for county attributes (household income, urbanicity), SPC characteristics (stage, subtype), and treatment. Among 230 370 persons with SPCs (58.4% male), 4.5% were Asian or Pacific Islander, 9.6% were Black, 6.4% were Hispanic, and 79.5% were White. A total of 109 757 cancer-related deaths (47.6%) and 18 283 CVD-related deaths (7.9%) occurred during a median follow-up of 54 months (IQR, 12-93 months). In baseline models, compared with the White population, the risk of cancer-related death overall was higher in the Black (HR, 1.21; 95% CI, 1.18-1.23) and Hispanic (HR, 1.10; 95% CI, 1.07-1.13) populations but lower in the Asian or Pacific Islander population (HR, 0.93; 95% CI, 0.90-0.96). When stratified by 13 SPC types, the risk of cancer-related death was higher for 10 SPCs in the Black population, with the highest HR for uterine cancer (HR, 1.87; 95% CI, 1.63-2.15), and for 7 SPCs in the Hispanic population, most notably for melanoma (HR, 1.46; 95% CI, 1.21-1.76). For CVD-related death, the overall HR was higher in the Black population (HR, 1.41; 95% CI, 1.34-1.49), with elevated risks evident for 11 SPCs, but lower in the Asian or Pacific Islander (HR, 0.75; 95% CI, 0.69-0.81) and Hispanic (HR, 0.90; 95% CI, 0.84-0.96) populations than in the White population. After further adjustments for county attributes and SPC characteristics and treatment, HRs were reduced for cancer-related death and for CVD-related death and associations in the same direction remained. In this cohort study of SPC survivors, the Black population had the highest risk of both death from cancer and death from CVD, and the Hispanic population had a higher risk of death from cancer than the White population. Attenuations in HRs after adjustment for potentially modifiable factors highlight opportunities to reduce survival disparities among persons with multiple primary cancers.

Multidirectional characterization of cellular composition and spatial architecture in human multiple primary lung cancers

Multiple primary lung cancers (MPLCs) pose diagnostic and therapeutic challenges in clinic. Here, we orchestrated the cellular and spatial architecture of MPLCs by combining single-cell RNA-sequencing and spatial transcriptomics. Notably, we identified a previously undescribed sub-population of epithelial cells termed as CLDN2+ alveolar type II (AT2) which was specifically enriched in MPLCs. This subtype was observed to possess a relatively stationary state, play a critical role in cellular communication, aggregate spatially in tumor tissues, and dominate the malignant histopathological patterns. The CLDN2 protein expression can help distinguish MPLCs from intrapulmonary metastasis and solitary lung cancer. Moreover, a cell surface receptor−TNFRSF18/GITR was highly expressed in T cells of MPLCs, suggesting TNFRSF18 as one potential immunotherapeutic target in MPLCs. Meanwhile, high inter-lesion heterogeneity was observed in MPLCs. These findings will provide insights into diagnostic biomarkers and therapeutic targets and advance our understanding of the cellular and spatial architecture of MPLCs.

Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer

BackgroundCancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung.MethodsExome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case–control association analyses were performed.ResultsAltogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations.ConclusionsWe have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.

A commentary on "plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer".

A commentary on "plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer".