Successful Treatment of Steroid-Refractory Immune Thrombocytopenia in a Patient Developing Multiple Myeloma While on Immune Checkpoint Inhibitor Therapy for Lung Cancer: A Case Report.

Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.

Case report of multiple primary cancers and results of genetic testing to preliminarily explore their pathogenesis.

The occurrence of multiple primary malignancies in a single patient has been relatively rare. We report here the case of a 71-year-old man with three primary tumors of lung cancer, intrahepatic cholangiocarcinoma, and prostate cancer, and a preliminary study of the mechanisms by which multiple primary tumors develop at the genetic level. Because of the late stage of the patient's condition, large tumor burden, and poor physical status, the patient survived only a few months. In the case presented herein, cholangiocarcinoma, lung cancer, and prostate cancer were found simultaneously, and the pathogenic sites are not related. Whole-exome sequencing was performed on the pathological tissues to explore the mechanism that may underlie multiple primary cancers at the genetic level. Several gene mutations were found in this case. They involved cell proliferation, cell cycle regulation, genetic stability, metabolism, cell invasion, angiogenesis, cell apoptosis, and other pathways. It can be preliminarily inferred that the mechanism underlying multiple primary tumors is related to the abnormality of tumor-promoting and suppressing pathways.

Emerging trends in the coexistence of primary lung Cancer and hematologic malignancy: a comprehensive analysis of clinicopathological features and genetic abnormalities.

BACKGROUND: The incidence of multiple primary cancers (MPC), especially involving primary lung cancer (PLC) and primary hematologic malignancies (PHM), is rising. This study aims to analyze clinicopathological features, gene abnormalities, and prognostic outcomes in individuals diagnosed with PLC-PHM MPC. METHODS: A retrospective analysis included 89 patients diagnosed with PLC-PHM MPC at the Respiratory or Hematology Departments of Ruijin Hospital from 2003 to 2022 (a total of 842,047 people). Next-generation sequencing (NGS) assessed lung cancer specimens, while Polymerase Chain Reaction (PCR) and NGS were used for hematologic malignancy specimens. Statistical analysis involved survival analysis and Cox regression. RESULTS: PLC-PHM MPC incidence surged from 1.67 per year (2011-2013) to 16.3 per year (2020-2022). The primary demographic for PLC-PHM MPC consists predominantly of elderly (average age 66 years) males (59.6%), with a high prevalence of metachronous MPC (89.9%). The prevailing histological types were lung adenocarcinoma (70.8%) in lung cancer (LC) and mature B-cell lymphomas (50.6%) in hematologic malignancies (HM). Notably, in a molecular testing cohort of 38 LC patients, 84.2% of lung cancer cases exhibited driver mutations, in which EGFR mutations frequence prevalent was 74.2%. In total group of 85 cases achieved a median overall survival (mOS) of 46.2 months, with a 5-year survival rate of 37.9% and advanced LC patients with LC gene mutations achieved a mOS was 52.6 months, with a 5-year OS rate of 30.6%. The median progression-free survival (PFS) following first-line treatment of 11 advanced patients with lung cancer-associated driver gene mutations is 26.6 months. Multivariate Cox regression revealed a favorable OS associated with surgery for LC, favorable PS score, adenocarcinoma pathology of LC, and the presence of genetic abnormalities associated with HM. CONCLUSION: PLC-PHM MPC incidence is rising, characterized by a significant proportion of lung adenocarcinoma and a high prevalence of positive driver genes, especially in EGFR. Despite suffering from two primary tumors, the PLC-PHM MPC patients had superior data of both PFS and OS, suggesting an inherently intricate background of genetic abnormalities between the two kinds of tumors.

BRCA2, PALB2, RECQL4 Germline Pathogenic Variants, and Somatic TP53 Mutation in Triple Metachronous Malignancies: A Case Report and Literature Review.

Background: Multiple primary cancer (MPC) refers to the presence of more than one cancer in an individual. Triple primary malignancies are uncommon. Case: We report the case of a 50-year-old postmenopausal woman in our gynecology department, diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. She carried germline mutations in BRCA2, PALB2, and RECQL4, along with a somatic pathogenic variant in TP53. Endometrial cancer patients harboring germline pathogenic variants in BRCA2 exhibit a heightened risk of ovarian and breast cancer. BRCA2 is known to play a role in the development of ovarian and breast cancer, while PALB2 is identified as a gene associated with breast cancer susceptibility. RECQL4 has been linked to breast cancer, cervical cancer, and other tumors. Conclusion: Genetic testing may be imperative for identifying MPC in endometrial cancer patients. For individuals with BRCA2 and other gene pathogenic variants, routine examination and monitoring of the endometrium, ovaries, breasts, and other sites prone to polygenic cancer are recommended.

Synchronous Double Primary Cancer Complicated With Severe Hypercalcemia.

Hypercalcemia of malignancy (HCM) is an important cancer-related medical emergency. It is a sign of advanced disease with a poor prognosis. We report a case of a 55-year-old man who presented with decreased sensorium, constipation for 4 days, dysphonia, and weight loss for the past three months. The physical examination showed a petrous nodular lesion of the neck in relation to the right sternocleidomastoid muscle. The digital rectal examination showed an enlarged prostate with a nodule of hard consistency. The blood revealed a hypercalcemia of 18.9 mg/dl and a prostate-specific antigen of 319.18 ng/ml. After further investigation, we discovered a squamous cell carcinoma of the larynx with multiple osteolytic bone lesions and a prostate adenocarcinoma. The hypercalcemia was treated with sodium pamidronate with good results. Such severe hypercalcemia demanded further research which revealed that not only the osteolytic lesions contributed to the elevation of calcium serum levels but also the tumor secretion of parathyroid hormone-related protein. This case highlights the importance of not only having a high suspicion for malignancy in patients presenting with hypercalcemia but also being aware of possible additional diagnoses in a patient with an already identified primary pathology.

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT).

PURPOSE/OBJECTIVES: Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT. MATERIALS/METHODS: Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing definitive SBRT, the imaging, and pathology for every patient were reviewed in a multi-disciplinary thoracic/pulmonary tumor board. Dose and fractionation varied with the most common prescriptions being 50 Gy/5 fractions, 56 Gy/4 fractions, and 55 Gy/5 fractions. RESULTS: A total of 38 patients with a total of 80 MPLCs were treated, among which 68 were T1 lesions and 12 were T2 lesions. Median follow-up was 25.9 months, with local control (LC) rates calculated per lesion to be 98.6%, 93.3%, and 88.2% at one, two, and three years. Median overall survival (OS) was 43.5 months; 83.6%, 67.8%, and 52.3% at one, two, and three years, respectively. Sixty-two of the 80 (77.5%) treated lesions were not associated with any subsequent acute or late toxicity. The 18 (22.5%) lesions associated with toxicity included nine acute and nine late events. All toxicity was either grade 1 (13 of 18) or grade 2 (five of 18). CONCLUSIONS: SBRT for early-stage MPLC achieves high control rates with limited toxicity. MPLC patients deemed unfit for open surgical management should be considered for definitive SBRT.

Survival and prognostic factors in patients with synchronous multiple primary esophageal squamous cell carcinoma receiving definitive radiotherapy: A propensity score-matched analysis.

Purpose: To compare the lesion characteristics and radiotherapy efficacy of patients with single and multiple esophageal squamous cell carcinoma (ESCC), to evaluate the effect of multiple lesions on ESCC, and establish a nomogram survival prediction model for patients with synchronous multiple primary esophageal squamous cell carcinoma (SMPESCC) who received definitive radiotherapy. Materials and methods: The study enrolled 1,034 patients with ESCC who underwent definitive radiotherapy between 2010 and 2020. The efficacy of radiotherapy was compared between 101 patients with SMPESCC and 933 patients with single ESCC. Propensity score matching was used to control for potential confounders. For patients with SMPESCC, a nomogram prediction model was established based on the Cox regression model. Results: The median OS was 30.00 (95% CI = 25.08-34.92) months for the single lesion group and 19.00 (95% CI = 15.51-22.48) months for the multiple cancer group respectively. Multivariate COX regression analysis showed that multiple cancer was an independent prognostic factor for ESCC patients (HR=1.89, 95%CI=1.49-2.38, P<0.001). Cox multivariate analysis of SMPESCC patients showed that T stage (P =0.002), chemotherapy (P =0.006), and lesion spacing (P =0.004) were independent prognostic factors associated with OS. The nomogram was established by combining T stage, chemotherapy, and lesion spacing, and Harrell's C index was 0.711 after internal cross-validation. The calibration curve and decision curve analysis confirmed that the nomogram survival prediction model had a good predictive value for individual survival. Conclusions: The survival rate of single esophageal cancer is significantly better than that of multiple lesions. Patients with SMPESCC exhibit worse survival than patients with single ESCC. Multiple lesions have a significant impact on the survival of patients with ESCC. The nomogram model established for SMPESCC patients can well predict the individual survival of patients.

The epidemiology of multiple primary cancers in Belgium (2004-2017): Incidence, proportion, risk, stage and impact on relative survival estimates.

BACKGROUND: As both life expectancy and cancer survival improve, the incidence of multiple primary cancer has augmented and is expected to further increase. This study describes for the first time the epidemiology of multiple invasive tumours in Belgium. METHODS: This nationwide study, based on all cancers diagnosed between 2004 and 2017 in Belgium, describes the proportion of multiple primary cancer, its evolution over time, the impact of inclusion or exclusion of multiple primary cancer on relative survival estimates, the risk of developing a second primary cancer, and the difference in stage between first and second primary cancer for the same patient. RESULTS: The proportion of multiple primary cancer increases with age, varies across cancer sites (from 4% for testis cancer to 22.8% for oesophageal cancer), is higher in men than in women, and has linearly increased over time. The inclusion of multiple primary cancer resulted in smaller 5-year relative survival and this impact is more pronounced in cancer sites with high relative survival. Patients with a first primary cancer have an increased risk to develop a new primary cancer compared to the population without a previous cancer history (1.27 and 1.59 times higher in men and women, respectively) and this risk depends on cancer site. Second primary cancers are associated with more advanced stages and more unknown stages than the corresponding first cancer diagnosis. CONCLUSIONS: This study describes multiple primary cancer according to several measures (proportion, standardised incidence ratio for an second primary cancer, impact of multiple primary cancer on relative survival and differences according to stage) for the first time in Belgium. The results are based on data of a population-based cancer registry with a relatively recent onset (2004).

Clinical and prognostic features of multiple primary cancers with oral squamous cell carcinoma.

OBJECTIVE: To characterize the epidemiological, clinical, and prognostic features of multiple primary cancers (MPC) following oral squamous cell carcinoma (OSCC). DESIGN: Data from the Surveillance, Epidemiology, and End Results Program database were analyzed to determine the standardized incidence ratio (SIR) of multiple subsequent sites, difference in clinical and prognostic features between MPC and single primary OSCC. RESULTS: The sites with the highest SIRs were the oral cavity (SIR = 69.48), other oral cavity and pharynx (SIR=55.46), pharynx (SIR=39.21), tonsils (SIR=33.52), trachea (SIR=33.24), esophagus (SIR=18.00), and larynx (SIR=13.12). The 5- and 10-year survival rates for single primary OSCC were 57.9% (95% CI: 56.7-59.2%) and 47.1% (95% CI: 45.7-48.6%), respectively, while those for MPC were 66.9% (95% CI: 64.6-69.4%) and 42.2% (95% CI: 39.5-45.2%), respectively. The mean age of MPC patients was significantly higher than that of single primary OSCC patients. MPC are more common in the gums and other sites of the oral cavity, and more likely to be detected in early TNM stage and pathological grade. Age, site, T-stage, and N-stage were significantly associated with prognosis of MPC. CONCLUSIONS: Significant differences in clinical and prognostic features were found between MPC and single primary OSCC. Considering MPC has a poor long-term prognosis, it is necessary to identify MPC and single primary OSCC early.

Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas.

BACKGROUND: Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC). METHODS: In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group). RESULTS: No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045). CONCLUSIONS: S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.

Familial risk associated with lung cancer as a second primary malignancy in first-degree relatives.

BACKGROUND: Aggregation of lung cancer (LCa) in family members is well-documented. However, little is known on the familial risk of LCa when first-degree relatives (FDRs, parents or siblings) are diagnosed with LCa as a second primary malignancy (LCa-2). We aimed to investigate whether and to what extent a family history of LCa-2 was associated with an increased LCa risk. METHODS: In this Swedish national cohort we identified 127,865 individuals who had one FDR affected by LCa as a first primary cancer (LCa-1) and 15,490 individuals who had one FDR affected by LCa-2, respectively. We then estimated relative risk (RR) of LCa using those without cancer family history as reference. RESULTS: The number of LCa-2 has been increasing annually and rather similarly in men and women in the last decade. Familial RR of LCa was 1.96 (95%, 1.85-2.07) for LCa-1 family history and 1.89 for LCa-2 (1.62-2.21). Risk was especially high when FDR was diagnosed with early-onset LCa-2 and when siblings were affected by LCa-2. The RR was 1.53 (1.10-2.12) when LCa-2 in FDR was diagnosed within 26 months after first primary cancer, and it increased to 2.16 (1.62-2.90) when LCa-2 was diagnosed between 74 to 154 months. Higher risk was observed for first primary cancer of the ovary (4.45, 1.85-10.7), nervous system (3.49, 1.45-8.38), upper aerodigestive tract (2.83, 1.78-4.49) and cervix (2.55, 1.41-4.61), and for non-Hodgkin lymphoma (3.13, 1.57-6.27). CONCLUSIONS: LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs.

Cancer Prevention for Survivors: Incidence of Second Primary Cancers and Sex Differences-A Population-Based Study from an Italian Cancer Registry.

BACKGROUND: The number of cancer survivors continues to increase, thanks to advances in cancer diagnosis and treatment. Unfortunately, the incidence of a second primary cancer (SPC) is also increasing, but limited studies reporting incidence data are available regarding multiple cancers. This study presents our observations on multiple primary malignant cancers, the associations between sites, and the inherent sex differences. PATIENTS AND METHODS: We report the data, disaggregated by sex, concerning the SPCs that were recorded in the "Registro Tumori Integrato" (RTI) a population-based cancer registry in Sicily, Italy, as observed in the period from 2003 to 2017, in a total population of approximately 2,300,000. SPCs were divided into synchronous and metachronous cancers. The International Classification of Diseases for Oncology, third edition (ICD-O-3), was used for topographical and morphological classifications. Multiple primary cancers with multi-organ primitiveness were selected from the database of the RTI by extracting patients with more than one diagnosis. SPCs had different histology or morphology from the particular cancer that was considered to be the index cancer case. Multicenter or multifocal cancers, or metastases, were excluded. The percentages of cancer by sex and topography, the average age of incidence, and a breakdown by age were computed. RESULTS: Differences were observed between sexes in terms of incidence and site for SPCs. The most frequent SPC was skin cancer (20% of the SPCs observed). The associations among sites of multiple cancers are reported. CONCLUSION: There are many gaps in our knowledge of sex differences in cancer. The study of multiple primary cancers could bring more likely opportunities for evaluation of the cancer burden and trends that can be used to identify new research areas by population health programs, as well as for clinical researchers.

Multiple primary cancers in men with sporadic or familial prostate cancer: Its clinical implications.

OBJECTIVE: To evaluate the risk of concordant cancers in patients with prostate cancer (CaP) and examine whether this risk differed according to family history of CaP. MATERIALS AND METHODS: We examined 1,102 patients with CaP , having prospectively acquired pedigrees, and analyzed information regarding multiple primary cancers. The prevalence of concordant cancers was assessed with respect to the family history of CaP . First-degree familial CaP was defined as a positive history of CaP in first-degree relatives (parents, siblings, and offspring). Odds ratios for each concordant cancer in men with first-degree familial CaP were estimated. Clinical characteristics were compared between men with and without concordant cancers. RESULTS: The prevalence of multiple primary cancers in sporadic PCa was 12.0%, similar to that of first-degree familial CaP (13.5%, P = 0.698). Gastrointestinal cancer was the most common concordant cancer (3.6%), followed by colorectal (2.9%), lung (1.5%), urothelial (1.3%), kidney (1.1%), and other cancers. Colorectal cancer was more frequent in first-degree familial CaP than in sporadic disease (6.8 vs. 2.7%, P = 0.045). However, the rates of other concordant cancers were similar between the 2 groups (P range, 0.242-0.963). Compared with sporadic disease, the age-adjusted odds ratio for concordant colorectal cancer in first-degree familial CaP was 2.930 (95% confidence interval, 1.082-7.929). Patients with concordant colorectal cancer had fewer (2.8 vs. 3.9 cores, P = 0.041) and a lower percentage of (23.5 vs. 33.1%, P = 0.030) positive biopsy cores than CaP only patients. CONCLUSIONS: A family history of CaP was significantly associated with a risk of concordant colorectal cancer. These findings imply that some CaP shares a genetic pathogenesis with colorectal cancer.

Colorectal cancer risk in association with colorectal cancer as a second malignancy in relatives: a nationwide cohort study.

BACKGROUND: Increasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk. METHODS: In this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group. RESULTS: A cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65-1.79) and 1.50 (1.32-1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system. CONCLUSIONS: Individuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships.

Simultaneous Presentation of Multiple Myeloma and Lung Cancer: Case Report and Gene Bioinformatics Analysis.

Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.

Comparative Genomic Analysis Reveals Genetic Variations in Multiple Primary Esophageal Squamous Cell Carcinoma of Chinese Population.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant tumors. The incidence of malignant transformation of esophageal mucosa increases greatly due to long-term exposure to factors such as smoking, drinking, and poor eating habits. Furthermore, multiple primary tumors could occur synchronously or asynchronously in the upper aerodigestive tract, especially in the esophagus, adding difficulty to the treatment of ESCC. Genetic mutations are important during the malignant transformation from normal mucosa to esophageal cancer, but the underlying mechanism has not been fully elucidated. In this study, we used whole-exome sequencing (WES) to profile genetic variations in physiologically normal mucosa (PNM) and ESCC tumors, as well as PNM of non-ESCC subjects. We found significant differences in mutation frequencies of NOTCH1 and NOTCH2, copy number variations (CNVs) at both gene and chromosomal arm levels, and cancer-related HIPPO, WNT, and NRF2 signaling pathways between ESCC tumors and normal mucosa. Our analysis of both primary tumors and paired PNM in bifocal ESCC revealed three different primary tumor evolution modes, and the most common mode exhibited a complete genomic divergence in all the samples from the same patient. Furthermore, the mutation frequency of TP53 was significantly higher in ESCC cases than that in non-ESCC cases. Overall, our results provide important evidence for further elucidating the mechanisms of genetic mutations underlying the cause of ESCC.

Multiple Primary Malignant Neoplasms in African Americans: A Case Series and Literature Review.

Multiple primary malignant neoplasms (MPMNs) or multiple primary malignancies are defined as two or more histologically distinct malignancies present in the same individual. While second or higher-order malignancies account for approximately 18% of all cancers in the United States, it is reasonable to presume that MPMNs are now occurring more frequently than previously reported. Underserved groups such as blacks and Hispanics may represent a high proportion of these underreported cases due to well-established health disparities. Although the role of health disparities has been well established in single primary malignancies, less is known on racial differences in patients with multiple primaries. In comparing MPMNs by race, blacks have lower survival rates compared to white patients. Moreover, despite the lower overall incidence of MPMNs in blacks compared to white patients, when broken down by the specific types of cancers and gender, there are significant racial disparities in the incidence of prostate cancer and possibly other cancers. Further research and case reports are required to explore the risk factors of developing MPMNs in these groups. Our case series explores three African American patients with MPMNs that are rarely described in the literature and outlines the management challenges of treating multiple malignancies.

Prostate cancer incidence and survival in relation to prostate cancer as second cancer in relatives.

OBJECTIVES: To investigate if the risk of prostate cancer (PC) differs based on the order of primary PC diagnosed in first-degree relatives (FDRs) given possibly different risk factors for PC as first primary cancer (PCa-1) and second primary cancer (PCa-2). SUBJECTS AND METHODS: In this Swedish nationwide cohort, PC diagnosis was followed for among 149,985 men with one FDR affected by PCa-1, 10,972 with one FDR affected by PCa-2 and 2,896,561 without any FDRs affected by cancer in a maximum of 57 years. PC patients were further followed for death due to PC since diagnosis. Relative risk (RR) of PC was estimated with Poisson regression and hazard ratio (HR) with Cox proportional hazard model. RESULTS: Compared to men without any FDRs affected by cancer, the RRs of PC in men with one FDR affected by PCa-1 and PCa-2 were 2.12 (95% confidence interval [CI]: 2.07-2.17) and 1.69 (1.54-1.85), respectively. The risk in men with one FDR affected by PCa-2 was significantly lower than those with one FDR affected by PCa-1 after additionally adjusting for family relationship (father-son and brothers) and age at diagnosis of PC in FDR (RR PCa-2 vs PCa-1 , 0.85, 95% CI, 0.78-0.94). PC patients with a family history of PCa-2 were more likely to be detected at late-stage and less likely to be diagnosed by screening, compared to those with a family history of PCa-1. Patients whose PC was diagnosed after the diagnosis of PCa-1 in FDRs had a better survival than those without a family history of cancer (HR, 0.88, 95% CI, 0.80-0.97), but no such association was observed among patients with a family history of PCa-2. CONCLUSION: Our study indicates a discrepancy between PC risks associated with a family history of PCa-1 and PC-2 and the reason behind it may be multifactorial.

A case of successful conversion surgery for locally advanced pancreatic cancer with synchronous triple cancer of the lung and esophagus: a case report.

BACKGROUND: The number of reports of multiple primary cancer (MPC) is increasing because of the advancement in diagnostic imaging technology. However, the treatment strategy for MPCs involving pancreatic cancer is controversial because of the extremely poor prognosis. We herein report a patient with synchronous triple cancer involving the pancreas, esophagus, and lung who underwent conversion surgery after intensive chemotherapy for unresectable locally advanced pancreatic cancer. CASE PRESENTATION: A 59-year-old man was admitted to our hospital with epigastric pain, anorexia, and weight loss. Computed tomography and upper gastrointestinal endoscopy revealed that the patient had synchronous triple cancer of the pancreas, esophagus, and lung. While the esophageal and lung cancer were relatively non-progressive, the pancreatic tail cancer had invaded the aorta, celiac axis, and left kidney, and the patient was diagnosed with unresectable locally advanced disease. Because the described lesion could have been the prognostic determinant for this patient, we initiated intensive chemotherapy (gemcitabine plus nab-paclitaxel) for pancreatic cancer. After six courses of chemotherapy, the tumor size shrank remarkably and no invasion to the aorta or celiac axis was observed. No significant changes were observed in the esophageal and lung cancers; endoscopic submucosal dissection could be still a curative treatment for the esophageal cancer. Therefore, we performed curative resection for pancreatic cancer (distal pancreatomy, splenectomy, and left nephrectomy; ypT3N0cM0, ypStage IIA, UICC 8th). Pathologically, complete resection was achieved. The patient then underwent endoscopic submucosal dissection for early esophageal cancer (pT1a[M]-LPM) and video-assisted thoracoscopic right upper lobectomy in combination with right lower partial resection for early lung cancer (pT2aN0M0, pStage IB, UICC 8th). Eight months after pancreatic cancer surgery, the patient is alive and has no sign of recurrence; as a result of the successful treatment, the patient has a good quality of life. CONCLUSIONS: Treatment of MPC is challenging, especially for cases with unresectable tumors. Although synchronous triple cancer can involve unresectable pancreatic cancer, radical resection may be possible after careful assessment of the appropriate treatment strategy and downstaging of unresectable tumors.