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This large Nordic series showed that gastrointestinal neuroendocrine carcinomas with a Ki-67 below 55 percent respond poorly to platinum-etoposide yet live longer than those above it, which led to the separation of grade 3 neuroendocrine tumours from carcinomas.
Retrospective analysis of 305 patients with advanced gastrointestinal high-grade (grade 3) neuroendocrine carcinoma treated at Nordic centres, examining response to first-line platinum-based chemotherapy and survival by clinical and pathological features.
Response to platinum chemotherapy was 42 percent for Ki-67 of 55 percent or more but 15 percent below it, while survival was longer in the lower Ki-67 group (median 14 versus 10 months); performance status, primary site and lactate dehydrogenase were also prognostic.
The 55 percent Ki-67 threshold and the recognition that well-differentiated grade 3 tumours behave differently from carcinomas, now embedded in the WHO classification, came from this analysis.