Analyses of sex-based clinicopathological differences among patients with gastrointestinal neuroendocrine neoplasms in Europe

Abstract

Background Previous studies have found variations in cancer types, tumor progression, and disease outcomes between men and women. However, there is limited knowledge of the effect of sex on gastrointestinal neuroendocrine neoplasms (GI-NENs). Methods We identified 1354 patients with GI-NEN from the IQVIA’s Oncology Dynamics database. Patients were derived from four European countries (Germany, France, the United Kingdom (UK), Spain). Clinical and tumor related characteristics including patients' age, tumor stage, tumor grading and differentiation, frequency and sites of metastases, as well as co-morbidities were analyzed as a function of patients´ sex. Results Among the 1354 included patients, 626 were female and 728 were male. The median age was similar between both groups (w: 65.6 years, SD: 12.1 vs. m: 64.7 years; SD: 11.9; p = 0.452). UK was the country with the most patients, however, there was no differences in the sex ratio between the different countries. Among documented co-morbidities, asthma was more often diagnosed in women (7.7% vs. 3.7%), while COPD was more prevalent in men (12.1% vs. 5.8%). The ECOG performance states was comparable between females and males. Of note, the patients´ sex was not associated with tumor origin (e.g., pNET or siNET). Females were overrepresented among G1 tumors (22.4% vs. 16.8%), however, median proliferation rates according to Ki-67 were similar between both groups. In line, no differences in tumor stages was found and rates of metastases as well as the specific sites of metastases were similar between males and females. Finally, no differences in the applied tumor specific treatments between the both sexes became apparent. Conclusion Females were overrepresented among G1 tumors. No further sex-specific differences became apparent, highlighting that sex-related factors might play a rather subordinate role in the pathophysiology of GI-NENs. Such data may help to better understand the specific epidemiology of GI-NEN.

Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study

“…Evaluating studies of varying intent (not aimed at evaluating gender differences or focused on CaS), women seemed to have improved outcomes, a slight advantage in response to therapy, especially for liver metastases, and better survival compared to men [ 3 , 18 – 21 , 43 – 46 ]. However, neither our study nor previous analyses revealed any gender-related differences in treatment modalities, response to therapy, and patient outcomes in NEN patients [ 4 , 42 ]. However, when evaluating the therapeutic outcomes, limitations of our study should be taken in account, mostly due to its retrospective nature, the relatively small sample size when subdividing patients according to therapy, and the partial overlap of patients between the treatment groups which could not allow a clear separation of therapeutic effects.…”

“…Our analysis did not reveal any significant differences in pathological grade, tumor stage, and distant metastases at diagnosis of CaS between men and women. Scarce data exist in the literature providing evidence that female patients are diagnosed with G1 and low G2 NEN more frequently that male patients [ 2 , 3 , 42 ], but data specifically focused on CaS are not available. In our study, the majority of patients were diagnosed with G1–G2 grading, and no statistically significant difference was found related to gender.…”

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives

“…Leoncini et al [ 17 ] systematically analyzed 11 studies involving 72,048 patients and reported that males exhibit a greater incidence of high-grade NENs. This finding was supported by other studies, which also demonstrated that males are more likely to develop malignant NENs [ 1 , 18 , 19 ]. Differences in dietary habits may contribute to differences in the incidence of GEP-NENs between males and females [ 20 , 21 ].…”

“…This allows for the detection of tumors by molecular imaging of SSTRs via radionuclide-labeled somatostatin analogs (SSAs), single-photon emission computed tomography (SPECT), or positron emission tomography (PET). The commonly used radionuclides in SPECT imaging are 99m Tc, 131 I, and 111 In, and the positron nuclides used in PET are 18 F and 68 Ga. To date, 68 Ga-DOTA-DSA PET/ CTs, such as 68 Ga-DOTATATE, 68 Ga-DOTANOC, and 68 Ga-DOTATOC PET/CTs, have been developed to diagnose GEP-NENs [85]. Several studies have proven that 68 Ga-DOTATATE PET/CT has high accuracy and has become the preferred strategy for diagnosing GEP-NENs [81,[86][87][88][89].…”

“…However, the value of 18 F-FDG PET/CT in the diagnosis of GEP-NENs is still controversial since GEP-NENs generally exhibit indolent biological behavior with low glycolytic activity. Several studies have reported that 18 F-FDG PET/CT has an acceptable diagnostic value for aggressive GEP-NENs with a Ki-67 index greater than or equal to 10% and low expression of SSTRs [91,92]. Recently, two imaging classifications of NENs were developed based on 68 Ga-DOTATATE and 18 F-FDG PET/CTs [93,94].…”