Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas

Kamp, Kimberly; Damhuis, Ronald; Feelders, Richard A; Herder, Wouter W. de

doi:10.1530/erc-11-0315

Cited by 44 publications

(42 citation statements)

References 15 publications

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“…Furthermore, breast malignancies accounted for 14.3% of additional primaries. These observations are consistent with a recently published study of a Dutch cohort and likely reflect the trend toward increased cancer surveillance over the last two decades combined with the fact that breast, prostate, lung, and colon cancers are among the most common cancers diagnosed in the U.S (Kamp et al 2012). Nevertheless, exogenous mitogenic effects of secretory products from a primary tumor causing neoplastic transformation as well as common environmental exposures or behavioral risk factors among a large number of cancers must also be considered (Neugut & Robinson 1992, Modlin et al 2003.…”

Section: Discussionsupporting

confidence: 91%

“…In our series, almost one-third (29%) of patients with SICs had an associated metachronous primary tumor, a finding consistent with what other investigators have reported for carcinoid tumors in general. Most recently, Modlin et al used the SEER database to show that carcinoid tumors of all types were associated with other non-carcinoid tumors in 22.4% of patients; however, other studies have reported associations with rates varying from 13.7 to 40.7% (Berge & Linell 1976, Saha et al 1989, Marshall & Bodnarchuk 1993, Kamp et al 2012. In the majority of these studies, the most common site of additional malignancy was the gastrointestinal tract, a finding not entirely reproduced by our data.…”

Section: Discussioncontrasting

confidence: 57%

“…As such, they have focused on gastrointestinal NETs in general, as opposed to more specifically SIC tumors. Most recently, Kamp et al (2012) published a review of 459 Dutch patients with NETs of the digestive tract and concluded that 13.7% of patients had a second primary cancer. Although a population-based study by Zar et al (2008) used the Swedish Cancer Registry to estimate excess risk associated with second primary malignancies (PM) among 3741 SIC patients, no study has used the US-based SEER database to quantify risk, none has investigated the predictors of additional malignancies in SIC patients, and none has utilized survival data to study differences in prognosis between SIC patients with and without additional PM.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

Amin¹,

Warner²,

Itzkowitz³

et al. 2012

Endocrine-Related Cancer

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Small-intestinal carcinoids (SIC) are the most common small-bowel malignancies. We sought to determine the risk of developing SIC before and after other primary malignancies (PM) and the prognosis of patients with SIC, with and without another PM. We used the Surveillance, Epidemiology, and End Results database to identify patients diagnosed with SICs between 1973 and 2007. Multiple primary-standardized incidence ratios were calculated as an approximation of relative risk (RR) to explore the association of SICs with metachronous malignancies. Survival analysis was performed using Kaplan-Meier methods and Cox proportional-hazard models. Among 8331 patients with SICs, 2424 (29%) had another PM at some time. The most common sites were prostate (26.2%), breast (14.3%), colon (9.1%), lung/bronchus (6.3%), and bladder (5.3%). Overall, 67% of patients had a PM diagnosed before SIC (pre-SIC), 33% after SIC (post-SIC), and 8% had a PM both before and after SIC. Among the pre-SIC group, the risk of future SIC was increased after cancers of the small bowel (RR 11.86 (95% CI: 6

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

Amin¹,

Warner²,

Itzkowitz³

et al. 2012

Endocrine-Related Cancer

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“…A number of reports have also demonstrated increased risk of additional malignancies occurring in the NET patient set [8,9,10,11,12,13,14], a factor which may add to the already challenging management of individuals with NET if coexistent. With the aforementioned relatively prolonged natural history of this tumour type, this presents a pertinent clinical consideration.…”

Section: Introductionmentioning

confidence: 99%

Incidence of Second Primary Malignancies in Patients with Neuroendocrine Tumours

Clift

Drymousis²,

Al‐Nahhas³

et al. 2015

Neuroendocrinology

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Background: An association between neuroendocrine tumours (NET) and increased risk of developing second primary malignancies (SPM) has been recognised. Methods: This was a retrospective review of our institutional prospectively maintained database of NET patients. We identified patients who had been diagnosed with both neuroendocrine and any additional malignancies via examination of patient notes. Results: Clinical data for 169 patients were analysed. After exclusion of patients known to have hereditary tumour predisposition syndromes, 29 SPM were identified in 26 patients (15.38%), the commonest being colorectal (n = 6), breast and renal carcinomas (both n = 5). SPM were classified as previous, synchronous or subsequent relative to NET diagnosis. Rates of SPM in pancreatic and small-bowel NET patients were comparable (15.7 vs. 19.6%, p = 0.78). A person-year methodology was used to compare observed numbers of SPM against expected values generated from age- and sex-specific incidence tables, with standardised incidence ratios (SIR) and 95% confidence intervals (CI) calculated. SPM incidence was significantly elevated in the synchronous subset (SIR 2.732, CI 1.177-5.382) whilst significantly fewer NET patients had a cancer history compared to the general population (SIR 0.4, CI 0.241-0.624). No overall differences were evident between observed and expected incidences of subsequent SPM (SIR 0.36, CI 0.044-1.051). The incidence of synchronous colorectal cancers was markedly elevated (SIR 13.079, CI 4.238-30.474). Conclusions: Our data support the use of colonoscopy in the diagnostic work-up of NET patients in anticipation of a colorectal SPM. The mechanistic underpinnings of this clinical phenomenon require further genetic investigation, and consideration of this knowledge in patient management pathways is warranted.

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“…The finding of an increased risk for SI-NETs associated with FH of breast cancer deserves further discussion. A first-degree FH of breast cancer has already been associated with an increased risk for CRC [32], but not for SI-NETs. The rate of metachronous breast cancer has also been reported to be higher than expected in patients with a previous diagnosis of NETs [10].…”

Section: Discussionmentioning

confidence: 99%

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

et al. 2015

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Background: The incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, but few studies have investigated risk factors for their occurrence, suggesting that family history (FH) of any cancer, smoking and previous cholecystectomy are associated with an increased risk. Such studies investigated small series or examined cancer registries without direct interviews. Aim: We therefore aimed at clarifying risk and protective factors for the occurrence of sporadic SI-NETs. Subjects and Methods: We performed a multicenter case-control study. Patients with a histologic diagnosis of SI-NETs were prospectively evaluated, excluding familial syndromes. Controls with non-neoplastic/non-chronic disorders seen at gastrointestinal outpatients clinics were matched for sex and age (4:1). All subjects were directly interviewed by means of a specific questionnaire on potential risk and protective factors. Cases and controls were compared by Fisher's test or Student's t test for categorical or continuous variables. Explanatory variables were analyzed by simple logistic regression analysis. A multiple logistic regression analysis was performed with an Enter model; p < 0.05 was considered significant. Results: 215 SI-NET patients and 860 controls were enrolled. FH of colorectal cancer (CRC) (8.8 vs. 5.0%) and breast cancer (10.2 vs. 4.8%), heavy smoking (24.7 vs. 14.8%) and drinking >21 alcohol units per week (7.4 vs. 3.8%) were all significantly more frequent in SI-NET patients than in controls. Multivariate analysis showed that FH of CRC (OR 2.23, 95% CI 1.29-3.84, p = 0.003), FH of breast cancer (OR 2.05, 95% CI 1.13-3.69, p = 0.01) and smoking (OR 1.47, 95% CI 1.07-2.03, p = 0.01) and in particular heavy smoking (OR 1.94, 95% CI 1.29-3.84, p = 0.0008) were associated with an increased risk for carcinoid occurrence, while use of aspirin can be considered a protective factor (OR 0.20, 95% CI 0.06-0.65, p = 0.008). Conclusion: FH of colorectal and breast cancer as well as smoking seem to be risk factors for the development of SI-NETs, while use of aspirin might be a protective factor. These factors partially overlap with those associated with CRC, but are different from those previously associated with pancreatic neuroendocrine tumors. These findings may suggest that the mechanisms of carcinogenesis for endocrine cells in different sites can be specific and similar to those of their exocrine counterparts.

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Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas

Cited by 44 publications

References 15 publications

The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

Incidence of Second Primary Malignancies in Patients with Neuroendocrine Tumours

Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study

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