Recent studies have indicated that systemic immune-inflammation and a poor nutritional status correlate with a poor prognosis in a lot of malignant tumors [20]. Malnutrition was very common in cancer patients whether surgical treatment or not. Onodera et al. first introduced PNI and they evaluated patients with gastric cancers undergoing surgeries with different catabolic state [21]. Two simple laboratory parameters-albumin and absolute lymphocyte count which were previously reported that these two parameters were associated with the prognosis of cancer, were used to evaluate the PNI [22]. Mounting evidence has indicated that low PNI is associated with poor prognosis in various types of malignancies. Meanwhile, it is stated by Proctor et al. that PNI can forecast the prognosis of malignancy regardless of the site of origin [23].
P-NEC is frequently associated with malnutrition, probably because of tumor growth and decreased oral intake due to abdominal pain. However, as far as we know there has been no relevant study on PNI in p-NEC. So far, in our study, we assessed the association of the nutrition-inflammation-based PNI with prognosis in p-NEC patients. Based on the results of the present study, we found that PNI could serve as independent predictors for p-NEC better than other parameters.
Our Kaplan-Meier analyses showed a positive correlation between PNI and p-NEC patients’ OS. In PNI-high group, the mean OS was longer than that in PNI-low group (P = 0.003). These results are consistent with several previous studies which evaluated the predictive role of PNI in a variety of malignancies [24–26].
In our cohort study, the most frequent symptoms of patients with p-NEC were weight loss and abdominal pain. Interestingly, in our present study, we found a close correlation between PNI and weight loss, and mean PNI in patients with weight loss was significantly lower than patients who has maintained their weight (P = 0.003). However, we found no significant relationship between PNI and abdominal pain.
Based on the results of current study, five prognostic factors, including age, abdomimal pain, weight loss, lymphatic metastasis and ENETs stage, predicted a poor prognosis following our univariate analysis. Next, these five parameters were used in multivariate analysis, and our results showed that PNI was an independent prognosticator in patients with P-NEC.
According to the WHO 2010 grade classification system, Ki-67 staining index was described as an independent predictor of clinical outcomes. Nevertheless, Bettini et al. published the opposite conclusion, in which the Ki-67 index was not demonstrated to have predictive value. GI-NEC patients with ki-67 < 55% were insensitive to platinum-based chemotherapy, but had a longer survival than patients with a higher Ki-67 staining index. A recent study on NEC reported that the survival time was somewhat more favorable in patients with a Ki-67 index of < 55% (median:14months) than in those with a Ki-67 index of ≧ 55% (median:10months). Based on these observations, we chose 55% as the Ki-67 cut-off value in this study. We found that the median surrival for p-NEC patients with Ki-67 staining index ≧ 55% was 3.5 months, while patients with Ki-67 staining index < 55% was 7months. Disappointingly, however, our study showed the OS between these two groups had no significant relationship (P = 0.105).
Because of properties of NEC of rapid progression, chemotherapy is usually given to patients with metastatic NEC. Based on two first-line chemotherapy studies published, the combination of cisplatin and etoposide is recommended as first-line therapy for metastatic NEC. In our study, only 30 patients (20.4 %) received postoperative adjuvant chemotherapy, the median survival of these patients was 7 months, while the median survival of patients with no chemotherapy was 6 months (p = 0.577).
However, this study still has some shortcomings. As a retrospective, single medical center study, it had its own drawback because of sample limitations. In future, a larger, prospective, randomized controlled research is needed to validate our results.
Taken together, our present study indicated that the PNI was an independent prognostic predictor of OS for p-NEC. A low PNI was associated with poor prognosis in p-NEC.