Increasing opportunities for breast-conserving therapy in multiple ipsilateral breast cancer: Dutch nationwide study.

INTRODUCTION: An increasing number of breast cancer patients undergo breast-conserving surgery (BCS), but multiple ipsilateral breast cancer (MIBC) is still considered a relative contraindication for breast conservation. This study provides an update on trends in the surgical management for MIBC over a 10-year period. METHODS: Nationwide data from the Netherlands Cancer Registration of all patients diagnosed with breast cancer between 2011 and 2021 were analysed. The primary outcomes of this study were the incidence of MIBC and the trend in breast surgery type among patients between 2011 and 2021. Secondary outcomes were the positive resection margin rates in patients treated with BCS, the proportion of patients requiring re-excision and overall survival. RESULTS: In total, 114 433 patients (83%) with unifocal breast cancer and 23 932 patients (17%) with MIBC were identified. The incidence of MIBC was stable (17%) over the years. Overall BCS rates, both primary and after neoadjuvant chemotherapy, increased in MIBC from 29% in 2011 to 41% in 2021. Re-excision was performed in 1348 patients (n = 8455, 16%). The 5-year OS estimate for patients with MIBC treated with BCS was 93%. The pathological complete response (pCR) in MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy was 23%. CONCLUSION: The breast conservation rate in MIBC has increased over the last decade. In addition, 23% of MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy achieved a pCR. This suggests increasing opportunities for even more BCS in MIBC.

Clinicopathological analysis of patients with dual malignancies: A retrospective study.

BACKGROUND: This study aims to report the increasing incidence of second primary malignancies to better understand the association of multiple primary cancers and the duration of their occurrence. Keeping in view the current trends in dual malignancies and to further emphasize the importance of screening and follow-up diagnosis, we reviewed the records of patients who were diagnosed with dual malignancies. MATERIAL AND METHODS: This is a retrospective observational study. We collected data from the hospital database, of patients presenting with either histologically proven synchronous or metachronous double primaries between January 1, 2017, and December 31, 2021. The time interval to differentiate between synchronous and metachronous has been taken as 6 months. RESULTS: During the period of five years, twenty-three patients presented with dual malignancy. Out of 23 cases, seven were synchronous (30.43%), and 16 were metachronous (69.56%). In the synchronous malignancy group, the most common site of first and second primary malignancy was breast [5 cases (71.4%) and 3 cases (42.8%), respectively]. In the metachronous malignancy group, the most common site of the first primary was breast (7 cases; 43.75%), followed by the head and neck (4 cases; 25%), and the most common site of the second primary was also the breast (6 cases; 37.5%), followed by the lung (5 cases; 31.25%). CONCLUSION: Second primary malignancies are not rare and can occur at any age. Regular follow-up and screening procedures by the treating oncologist can play a major role in early detection followed by appropriate treatment of second primary tumors.

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

BACKGROUND: 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. AIM: The aim of this study is to study the epidemiologic characteristics of multiple primary cancers in the eastern region of India. MATERIALS AND METHOD: 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. RESULT: 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. CONCLUSION: 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.

Epidemiology, Pattern, and Survival of Multiple Primary Malignant Neoplasms in Southeast Iran: Results of Kerman Population-Based Cancer Registry 2014-2020.

PURPOSE: Cancer survivors may experience a subsequent primary cancer that affects their survival and quality of life. This study aimed to investigate the epidemiology of multiple primary malignant neoplasms (MPMNs) in Kerman province, southeast Iran during 2014-2020. MATERIALS AND METHODS: In this retrospective cohort study, all patients who had been diagnosed with primary cancers and registered with the Kerman Cancer Registry Program (KPBCR) during 2014-2020 were included. MPMNs were defined as primary malignant tumors arising in different sites and/or were of different histological or morphological origins. If the second malignancy was diagnosed within the first six months from the diagnosis of the first tumor it was considered synchronous, and if after six months it was defined as metachronous. Logistic regression was used to analyze the relationship between age, sex, and primary cancer site with incidence and survival of secondary in the entire population. RESULTS: Of 26,315 patients registered with a primary cancer diagnosis, 492 (1.86%) developed subsequent primary cancers. The most common type of secondary cancer was skin and mucosa (n=131, 26.63%) followed by urogenital (n=115, 23.37%), followed by, gastrointestinal (n=62, 14.45%), and breast neoplasms (n=57, 11.59%). Most patients had metachronous tumors (n=350, 71.13%). The primary cancer site (Skin and mucosa, urogenital, and breast) was significantly associated with developing subsequent cancer among cancer survivors. The overall 5-year survival of MPMNs cases was over 50%. Older age at diagnosis (HR= 1.02) and having synchronous tumors (HR=1.41) were negatively associated with the survival time of patients with MPMNs. CONCLUSION: Both patients and physicians should be taught about the importance of prevention and the provision of care and screening services among cancer survivors. Studying the epidemiology, susceptibility, and risk factors of MPMNs among cancer survivors will open windows to a better understanding of this phenomenon and policy making.

Synchronous or metachronous breast and colorectal cancers in younger-than-average-age patients: a case series.

BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

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.

Multiple neoplasms in patients with uveal melanoma: a systematic review.

PURPOSE: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. METHODS: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. RESULTS: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. CONCLUSION: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

BACKGROUND: Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. METHODS: We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). RESULTS: Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. CONCLUSION: DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

The Burden of Multiple Basal Cell Carcinomas: A Population-wide Study.

Basal cell carcinoma (BCC) is a common skin cancer type and affected individuals are known to be at risk of developing multiple consecutive tumours. Research into BCC multiplicity has, thus far, been challenging, due to a lack of national registration. This registry-based cohort study aimed to analyse the occurrence of multiple BCCs in Sweden, and risk factors for subsequent primary BCCs. Data regarding all histopathologically verified, primary BCC tumours in Sweden from 2004 to 2017 was extracted from the Swedish BCC Registry. Risk of developing a subsequent BCC in relation to person-related factors was estimated with Cox regression analysis. Cumulative risk of BCC development after 1 or 3 earlier BCCs was estimated. In total, 39.9% of individuals with a registered BCC had at least 2 registered tumours. The risk of developing a subsequent BCC increased significantly in males, older age, and with residence in southern Sweden. The cumulative 5-year risk of developing an additional BCC after first diagnosis was approximately 30% in males and 27% in females and increased after multiple previous BCCs. This study showed the cumulative risk of a subsequent BCC to increase with a history of multiple BCCs, indicating the need for clinical surveillance in these individuals.

Triple Primary Cancers: An Analysis of Genetic and Environmental Factors.

The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk. PREVENTION RELEVANCE: In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility. See related Spotlight, p. 193.

Characterizations of uveal melanoma patients with three additional primary malignancies.

PURPOSE: In a population-based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies. METHOD: A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies. RESULTS: After more than 20 years of follow-up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different. CONCLUSION: Patients with UM may be diagnosed with non-ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow-up of the UM patients seems necessary. The UM is not always the main problem.

Simultaneous melanomas in the setting of multiple primary melanomas.

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

A pancancer analysis of the clinical and genomic characteristics of multiple primary cancers.

Multiple primary cancer (MPC) denotes individuals with two or more malignant tumors occurring simultaneously or successively. Herein, a total of 11,000 pancancer patients in TCGA database (1993-2013) were divided into MPC or non-MPC groups based on their history of other malignant tumors. The incidence of MPC has risen to 8.5-13.1% since 2000. Elderly individuals, males, early-stage cancer patients, and African Americans and Caucasians are identified as independent risk factors (p < 0.0001). Non-MPC patients exhibit significantly longer overall survival (OS) and disease-free survival (DFS) (p = 0.0038 and p = 0.0014). Age (p < 0.001) and tumor staging at initial diagnosis (p < 0.001) contribute to this difference. In our center, MPC was identified in 380 out of 801 tumor events based on SEER criteria. The peak occurrence of secondary primary was about 1-5 years after the first primary tumor, with a second small peak around 10-15 years. Multiple tumors commonly occur in the same organ (e.g., breast and lung), constituting 12.6%. Certain cancer types, notably skin cutaneous melanoma (SKCM), exhibit significantly higher tumor mutational burden (TMB) in the MPC group (17.31 vs. 6.55 mutations/MB, p < 0.001), with high TMB associated with improved survival (p < 0.001). High TMB in MPC may serve as a predictor for potential immunotherapy application.

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

OBJECTIVE: Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. METHODS: From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. RESULTS: During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. CONCLUSIONS: Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

Synchronous and metachronous neoplasms of different histogenesis with gastrointestinal stromal tumor (GIST): 10 years experience of a single institution.

AIM: Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal neoplasms of the gastrointestinal tract. Significant advances have been made in its pathogenesis, diagnosis, and treatment over the past few decades. However, little is known about the occurrence of synchronous or methacronous tumors with other histogenesis in addition to GISTs. The aim of this study was to present a series of 15 patients diagnosed with a second primary neoplasm in addition to GIST. MATERIAL AND METHODS: Patients who were diagnosed with both GIST and other primary neoplasm between January 2010 and December 2019 were included in the study. Demographic, clinicopathologic and immunohistochemical parameters of the patients were analyzed along with the follow-up results RESULTS: This study included 12 men and 3 women with a median age of 68 years (range: 57-83 years). Of the GISTs, 93.3% were localized in the stomach and 73.3% were at very low / low risk category. Of the second primary tumors, 66.6% were in the gastrointestinal tract. Detection of the GIST was synchronous in 9 cases, metachronous in 2 cases and preceded the GIST diagnosis in 4 cases. GIST was incidentally found intra-operatively in 3 of the cases. The mean size of the synchronous GISTs was 20 mm while the most common GIST-associated malignancy was gastric adenocarcinoma. The median follow-up times was 62 months (range: 13-129 months). CONCLUSIONS: The prevalence of secondary malignancies in GIST patients is significantly higher than the healthy population. The high occurrence rate of additional primary tumors in GIST patients has focused the attention of surgeons on this problem. While it is not yet clear if there is a causal association or a common genetic mechanism for the concomitant occurrence of GIST with other malignancies, a closer surveillance of GIST patients is needed due to their proved increased prevalence of a second primary tumor especially during the first year after diagnosis. KEY WORDS: Gastrointestinal stromal tumor, Coexistence, Synchronous malignancy, Second neoplasm, Gastric adenocarcinoma.

Risk of Multiple Primary Cancers in Patients With Merkel Cell Carcinoma: A SEER-Based Analysis.

Importance: The risk of subsequent primary cancers after a diagnosis of cutaneous Merkel cell carcinoma (MCC) is not well established. Objective: To evaluate the risk of subsequent primary cancers after the diagnosis of a first primary cutaneous MCC. Design, Setting, and Participants: This cohort study analyzed data from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from January 1, 2000, to December 31, 2019. In all, 6146 patients diagnosed with a first primary cutaneous MCC were identified. Main Outcomes and Measures: The primary outcome was the relative and absolute risks of subsequent primary cancers after the diagnosis of a first primary MCC, which were calculated using the standardized incidence ratio (SIR; ratio of observed to expected cases of subsequent cancer) and the excess risk (difference between observed and expected cases of subsequent cancer divided by the person-years at risk), respectively. Data were analyzed between January 1, 2000, and December 31, 2019. Results: Of 6146 patients with a first primary MCC diagnosed at a median (IQR) age of 76 (66-83) years, 3713 (60.4%) were men, and the predominant race and ethnicity was non-Hispanic White (5491 individuals [89.3%]). Of these patients, 725 (11.8%) developed subsequent primary cancers, with an SIR of 1.28 (95% CI, 1.19-1.38) and excess risk of 57.25 per 10 000 person-years. For solid tumors after MCC, risk was elevated for cutaneous melanoma (SIR, 2.36 [95% CI, 1.85-2.97]; excess risk, 15.27 per 10 000 person-years) and papillary thyroid carcinoma (SIR, 5.26 [95% CI, 3.25-8.04]; excess risk, 6.16 per 10 000 person-years). For hematologic cancers after MCC, risk was increased for non-Hodgkin lymphoma (SIR, 2.62 [95% CI, 2.04-3.32]; excess risk, 15.48 per 10 000 person-years). Conclusions and Relevance: This cohort study found that patients with MCC had an increased risk of subsequently developing solid and hematologic cancers. This increased risk may be associated with increased surveillance, treatment-related factors, or shared etiologies of the other cancers with MCC. Further studies exploring possible common etiological factors shared between MCC and other primary cancers are warranted.

Synchronous and metachronous multiple primary cancers in melanoma survivors: a gender perspective.

Background: Long-term survivors of cutaneous malignant melanoma (CMM) risk subsequent malignancies due to both host-related and environmental risk factors. This retrospective population-based study differentially assesses the risk of synchronous and metachronous cancers in a cohort of CMM survivors stratified by sex. Methods: The cohort study (1999-2018) included 9,726 CMM survivors (M = 4,873, F = 4,853) recorded by the cancer registry of all 5,000,000 residents in the Italian Veneto Region. By excluding subsequent CMM and non-CMM skin cancers, the incidence of synchronous and metachronous malignancies was calculated according to sex and tumor site, standardizing for age and calendar year. The Standardized Incidence Ratio (SIR) was calculated as the ratio between the number of subsequent cancers among CMM survivors and the expected number of malignancies among the regional population. Results: Irrespective of the site, the SIR for synchronous cancers increased in both sexes (SIR = 1.90 in males and 1.73 in females). Both sexes also demonstrated an excess risk for synchronous kidney/urinary tract malignancies (SIR = 6.99 in males and 12.11 in females), and women had an increased risk of synchronous breast cancer (SIR = 1.69). CMM male survivors featured a higher risk of metachronous thyroid (SIR = 3.51, 95% CI [1.87, 6.01]), and prostate (SIR = 1.35, 95% CI [1.12, 1.61]) malignancies. Among females, metachronous cancers featured higher SIR values than expected: kidney/urinary tract (SIR = 2.27, 95% CI [1.29, 3.68]), non-Hodgkin's lymphoma (SIR = 2.06, 95% CI [1.24, 3.21]), and breast (SIR = 1.46, 95% CI [1.22, 1.74]). Females had an overall increased risk of metachronous cancers in the first 5 years after CMM diagnosis (SIR = 1.54 at 6-11 months and 1.37 at 1-5 years). Conclusion: Among CMM survivors, the risk of metachronous non-skin cancers is higher than in the general population and differs significantly by sex. These results encourage sex-tailored interventions for metachronous secondary cancer prevention.

Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer.

Importance: The incidence of early-onset colorectal cancer (CRC) (age, <50 years) continues to increase globally within high-income countries. Objective: To examine and compare rates of synchronous neoplasia found in patients at colonoscopic diagnosis of early-onset CRC with rates found at diagnosis of average-onset CRC. Design, Setting, and Participants: In this multisite retrospective and cross-sectional study conducted at Mayo Clinic sites and in the Mayo Clinic Health System from January 1, 2012, to December 31, 2022, 150 randomly selected patients with early-onset CRC were identified from the electronic health record and matched with 150 patients with average-onset CRC based on sex and colonoscopic indication. Patients with known hereditary syndromes, past history of CRC, or inflammatory bowel disease were excluded. Main Outcomes and Measures: Colonoscopic findings (polyp size, number, site) and related histopathologic findings (adenoma, advanced adenoma, sessile serrated polyp) were analyzed in association with cancer clinicopathologic features and molecular data (mismatch repair status, KRAS, and BRAFV600E). Results: Among 300 patients (156 men [52%]), the median age at diagnosis was 43 years (IQR, 39-47 years) for those with early-onset CRC and 67 years (IQR, 57-76) for those with average-onset CRC. Overall, 85% of patients were symptomatic at CRC diagnosis. Cancer stage, grade, molecular features, body mass index, and family history did not differ significantly between these groups. Among patients with colon cancer, the overall prevalence of synchronous neoplasia was similar, yet advanced adenomas were 3 times more frequent in those with early-onset vs average-onset cancers (31 of 75 [41%] vs 10 of 75 [13%]; P < .001). This difference was not associated with cancer stage or primary location. Among patients with rectal cancer, nonadvanced adenomas were less frequent among the early-onset group than the average-onset group (21 of 75 [28%] vs 36 of 75 [48%]), and although the prevalence of advanced adenomas was similar (11 of 75 [15%] vs 14 of 75 [19%]), they were more commonly located in the rectum (early onset, 5 of 11 [45%] vs average onset, 1 of 14 [7%]). Patients with early-onset cancer of the colon were significantly more likely than those with early-onset cancer of the rectum to have a synchronous advanced adenoma (31 of 75 [41%] vs 11 of 75 [15%]; P < .001). Conclusions and Relevance: In this cross-sectional study, synchronous advanced adenomas were more commonly found in patients with early-onset colon cancer compared with average-onset colon cancer, and they were distributed throughout the colon. In contrast, advanced adenomas were not increased in patients with rectal cancer and, when detected, were predominantly located in the rectum.

Multiple primary melanomas: A literature review.

Survival rates for melanoma have increased in recent years, a higher number of patients survive after diagnosis, and, therefore, are at an increased risk of developing second primary melanoma. The aim of this literature review is to identify and integrate the incidence rates and other characteristics of multiple primary melanomas. A total of 36 independent studies were included in this review. The incidence of multiple primary melanomas reported ranged from 1.1% to 20.4%. Synchronous melanomas account for 5% to 66% of the reported lesions. The most common site for both first and subsequent melanomas is the trunk. Superficial spreading melanoma is the most common histological type in both first and subsequent primary melanoma. Regarding the mean Breslow index, subsequent melanomas appeared to be thinner than first melanomas. Our review suggests that melanoma patients are at a higher risk of developing a second primary melanoma and long-term surveillance is needed.