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Five species of Prionospio Malmgren, 1867, each with four pairs of branchiae, are studied from coast of the Iberian Peninsula. Two of these species, Prionospio cristaventralis sp. n. and P. parapari sp. n., are new to science, whereas P. caspersi Laubier, 1962, P. fallax Söderström, 1920, and P. ehlersi Fauvel, 1928 have been previously recorded. Prionospio cristaventralis sp. n. is characterized by having ventral crests present on chaetigers XI–XIX, dorsal crests and low crests on chaetigers X–XXXIV, triangular neuropodial postchaetal lamellae with pointed ventral edges on chaetiger II, oval neuropodial lamellae on chaetiger III, digitiform pinnules on the posterior face of the first and fourth pairs, and branchial pairs II and III are triangular. Prionospio parapari sp. n. is characterized by having rounded neuropodial postchaetal lamellae on chaetiger I, digitiform pinnules on the posterior face of the first and fourth pairs, branchial pairs II and III are cirriform, low dorsal crests on chaetigers VIII–IX, and oval neuropodial lamellae with enlarged dorsal edges on chaetiger III. A key is given to all Prionospio species with four pairs of branchiae known from the Iberian Peninsula coastline.

Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.

Abstract Background The Janus kinase/signal transducer and activator of transcription (JAK‐STAT) signaling pathway plays a key role in the systemic inflammatory response in many cancers, including colorectal cancer (CRC). This study evaluated the addition of ruxolitinib, a potent JAK1/2 inhibitor, to regorafenib in patients with relapsed/refractory metastatic CRC. Methods In this two‐part, multicenter, phase 2 study, eligible adult patients had metastatic adenocarcinoma of the colon or rectum; an Eastern Cooperative Oncology Group performance status of 0‐2; received fluoropyrimidine, oxaliplatin, and irinotecan‐based chemotherapy, an anti‐vascular endothelial growth factor therapy (if no contraindication); and if KRAS wild‐type (and no contraindication), an anti‐epidermal growth factor receptor therapy; and progressed following the last administration of approved therapy. Patients who received previous treatment with regorafenib, had an established cardiac or gastrointestinal disease, or had an active infection requiring treatment were excluded. The study was conducted in 95 sites in North America, European Union, Asia Pacific, and Israel. After an open‐label, safety run‐in phase (part 1; ruxolitinib 20 mg twice daily [BID] plus regorafenib 160 mg once daily [QD]), the double‐blind, randomized phase (part 2) was conducted wherein patients were randomized 1:1 to receive ruxolitinib 15 mg BID plus regorafenib 160 mg QD [ruxolitinib group] or placebo plus regorafenib 160 mg QD [placebo group]. Part 2 included substudy 1 (patients with high systemic inflammation, ie, C‐reactive protein [CRP] >10 mg/L) and substudy 2 (patients with low systemic inflammation, ie, CRP ≤10 mg/L); the primary endpoint was overall survival (OS). Results The study was terminated early; substudy 1 was terminated for futility at interim analysis and substudy 2 was terminated per sponsor decision. Ruxolitinib 20 mg BID was well tolerated in the safety run‐in (n = 11). Overall, 396 patients were randomized (substudy 1: n = 175 [ruxolitinib group, n = 87; placebo group, n = 88]; substudy 2: n = 221 [ruxolitinib group, n = 110; placebo group, n = 111]). There was no significant difference in OS or progression‐free survival (PFS) between treatments in substudy 1 (OS: hazard ratio [HR] = 1.040 [95% confidence interval: 0.725‐1.492]; PFS: HR = 1.004 [0.724‐1.391]) and substudy 2 (OS: HR = 0.767 [0.478‐1.231]; PFS: HR = 0.787 [0.576‐1.074]). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib were identified. Conclusions Although addition of ruxolitinib to regorafenib did not show increased safety concerns in patients with relapsed/refractory metastatic CRC, this combination did not improve OS/PFS vs. regorafenib plus placebo.