Does knowledge of the primary tumour affect survival after surgery for spinal metastatic disease? A retrospective longitudinal cohort study

ObjectivesTo compare survival after surgery for patients with spinal metastatic disease with known primary tumour (KPT) versus patients with unknown primary tumour (UPT).Participants393 patients 18 years or older (270 men and 123 women, mean age 67.3 years) undergoing surgery at Uppsala University Hospital in Swedenbetween 2006 and 2016due to spinal metastatic disease . 271 patients (69%) had a KPT at the time of surgery and 122 (31%) had an UPT.InterventionsDecompressive and/or stabilising spine surgery due to spinal metastatic disease.Primary outcomeSurvival (median and mean) after surgery.ResultsThe estimated median survival time after surgery for patients with KPT was 7.4 months (95% CI 6.0 to 8.7) and mean survival time was 21.6 months (95% CI 17.2 to 26.0). For patients with UPT, the median estimated survival time after surgery was 15.6 months (95% CI 7.5 to 23.7) and the mean survival time was 48.1 months (95% CI 37.3 to 59.0) (Breslow, p=0.001). Unknown primary cancer was a positive predictor of survival after surgery (Cox regression, HR=0.58, 95% CI 0.46 to 0.73).ConclusionIn this study, patients with spinal metastasis and UPT had a longer expected survival after surgery compared with patients with KPT. This suggests that patients with UPT and spinal metastasis should not be withheld from surgery only based on the fact that the primary tumour is unknown.

Primary versus secondary nature of mesenteric neuroendocrine tumours

Neuroendocrine tumours (NETs) are rare group of malignancy that originate from neuroendocrine cells present throughout the body. Most patients with NET first present with symptoms associated with metastasis, and up to 20% of patients have unknown primary site of tumour. Most common metastatic sites for small intestine NETs (SI-NETs) are the locoregional lymph nodes and liver. Although mesenteric metastasis through direct extension or lymphatic spread from SI-NETs is common, mesenteric extranodal involvement is extremely rare, and its biology and primary versus secondary nature are not well understood. Due to their small size and location, SI-NETs are frequently undetected on anatomical imaging or indium-111-pentetreotide single-photon emission computed tomography/CT (Octreoscan) and are difficult to be found via endoscopy. Gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography (68Ga-DOTATATE PET)/CT has been increasingly used for accurate staging, unknown primary tumour site localisation and appropriate management planning. We present a case of an incidentally found mesenteric NET with occult SI-NETs localised preoperatively by 68Ga-DOTATATE PET/CT.

Brain Metastasis from Unknown Primary Tumour: Moving from Old Retrospective Studies to Clinical Trials on Targeted Agents

Brain metastases (BMs) are the most common intracranial tumours in adults and occur up to 3–10 times more frequently than primary brain tumours. BMs may be the cause of the neurological presenting symptoms in patients with otherwise previously undiagnosed cancer. In up to 15% of patients with BMs, the primary tumour cannot be identified. These cases are known as BM of cancer of unknown primary (CUP) (BM-CUP). CUP has an early and aggressive metastatic spread, poor response to chemotherapy, and poor prognosis. The pathogenesis of CUP seems to be characterized by a specific underlying pro-metastatic signature. The understanding of BM-CUP, despite its relative frequency and unfavourable outcome, is still incomplete and clear indications on management are missing. Advances in diagnostic tools, molecular characterization, and target therapy have shifted the paradigm in the approach to metastasis from CUP: while earlier studies stressed the importance of finding the primary tumour and deciding on treatment based on the primary diagnosis, most recent studies focus on the importance of identifying targetable molecular markers in the metastasis itself. The aim of this review is to summarize current evidence on BM-CUP, from the diagnosis and pathogenesis to the treatment, with a focus on available studies and ongoing clinical trials.

Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival.