Clinical Behavior of Combined Versus Pure High-Grade Neuroendocrine Carcinoma

BackgroundThe aim of this study was to investigate and compare the clinical behaviors of combined and pure high-grade neuroendocrine carcinoma (large-cell neuroendocrine carcinoma [LCNEC] and small-cell lung carcinoma [SCLC]).Patients and MethodsData of 132 patients who underwent complete resection for combined or pure high-grade neuroendocrine carcinoma (combined group, 67; pure group, 65) between January 2001 and December 2015 were retrospectively reviewed. The clinicopathological features were analyzed and compared, and the prognoses were assessed by performing the Kaplan–Meier method and Cox regression analysis.ResultsThe combined and pure groups had nearly equivalent clinicopathological characteristics, specifically, older males with smoking history, almost the same percentage of pleural/lymphatic/vascular invasion, and nearly the same recurrence rates and relapse patterns.The combined group had prognosis equivalent to that of the pure group (5-year overall survival [OS] rates: 61.8% vs. 52.2%, respectively; P = .82 and 5-year recurrence-free survival [RFS] rates: 42.4% vs. 43.9%, respectively; P = .96), and this trend was identified in sub-analyses only for patients with LCNEC, SCLC, and the same pathological stage.Multivariable Cox regression analysis in patients with high-grade neuroendocrine carcinoma revealed that vascular invasion and pathological stage were independent prognostic factors for OS; more importantly, combined and pure histologies were proven to have nearly equivalent associations with prognosis (hazard ratio, 0.96; 95% confidence interval, 0.22to 1.66; P = .96).ResultsCombined high-grade neuroendocrine carcinoma had clinical behavior equivalent to those of pure high-grade neuroendocrine carcinoma, with similar clinicopathological characteristics.     

Pathology and Surgical Treatment of High-Grade Pancreatic Neuroendocrine Carcinoma: an Evolving Landscape

Pancreatic neuroendocrine neoplasms (PNENs) are rare, accounting for less than 5 % of all pancreatic tumors. High-grade pancreatic neuroendocrine carcinomas (hgPNECs) represent about 5 % of all PNENs. They show highly aggressive behavior with dismal prognosis. Throughout the last two decades, there has been a notable progress in basic and clinical research of PNENs and a therapeutic trend towards both more aggressive and minimally invasive surgery. Despite these advances, hgPNECs as a distinct clinical entity remains largely unexplored among surgeons. This review of current development in pathology reporting and surgical treatment of hgPNECs aims at increasing the awareness of an evolving field in pancreatic surgery.     

Systemic Therapy for Pancreatic Neuroendocrine Tumors

Patients with metastatic or advanced pancreatic neuroendocrine tumors (NETs) carry poorer prognoses relative to patients with other NETs due to bulkier and often, more proliferative baseline disease. Patients with these tumors also possess more approved treatment options relative to patients with other NETs, making therapeutic sequencing nuanced. As such, defining optimal therapeutic sequencing and developing more potent cytoreductive treatments for patients are significant areas of research need in the field. Herein this review, we discuss the current systemic therapy landscape, our approach to therapeutic sequencing in the clinic and ongoing studies seeking to define optimal sequencing of systemic therapies, and novel therapeutics in development, for patients with pancreatic NETs. We limit the scope of this latter topic to agents with preclinical or clinical rationale over the last 8 years to provide a contemporary view of the drug development landscape and focus primarily on new types of peptide receptor radionuclide therapy, anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors and anti-vascular endothelial growth receptor tyrosine kinase inhibitor plus immunotherapy combinations.     

Clinical Pathways for Pancreatic Neuroendocrine Tumors

Background

Pancreatic neuroendocrine tumors (PNETs) represent a group of diseases that pose diagnostic and therapeutic challenges due to their clinical and pathological heterogeneity as well as the limited number of patients available for clinical trials. Over the last couple of decades, a major progress in understanding tumor biology led to the discovery of new potential targets for the medical treatment of these tumors.

Discussion

There are numerous novel targeted agents in various stages of preclinical and clinical development that offer considerable promise as monotherapy or combination therapy for PNETs. The question of whether traditional clinical research methods are appropriate for the development of novel, targeted anticancer agents has been the subject of many discussions. Major challenges include identifying a valid target, the most effective agent within a target class, the right subset of population to benefit from the drug, and the most appropriate setting to use the drug. As new agents emerge, oncologists are faced with making clinical decisions sometimes before having a high level of evidence. In this review, we attempt to address some of the management steps involved in treating patients with pancreatic neuroendocrine tumors, particularly well to moderately differentiated tumors. The purpose of this review is to offer a therapeutic sequence including surgery, liver-directed therapy, chemotherapy, and targeted therapy for this disease.     

Clinical Benefit Assessment of Vismodegib Therapy in Patients With Advanced Basal Cell Carcinoma

Purpose.

Vismodegib was approved for the treatment of advanced basal cell carcinoma (aBCC) based on the pivotal ERIVANCE BCC study. The primary endpoint (objective response rate [ORR]) was assessed 9 months after the last patient was enrolled. To confirm the clinical benefit of vismodegib, an additional analysis was performed 12 months after the primary analysis.

Materials and Methods.

ERIVANCE BCC was a multicenter, nonrandomized, two-cohort study of 104 patients with histologically confirmed aBCC. Patients received 150 mg oral vismodegib daily until disease progression, intolerable toxicity, or withdrawal. An independent review panel comprising three expert clinicians reviewed patient photographs individually and as a consensus panel to evaluate baseline disease severity and clinical benefit after vismodegib treatment in 71 patients with locally advanced BCC (laBCC).

Results.

Sixty-three patients were efficacy evaluable; baseline and postprogression photographs for 61 were available for review. Baseline disease severity was judged as 5 or 4 (very severe or moderately severe) in 71.4%. Clinical benefit was observed in 76.2% (significant: 65.1%; some: 11.1%). Interpanelist agreement (maximum difference ≤1 point among panelists’ scores in 65.1% and 87.3% of patients for clinical benefit and baseline disease severity, respectively) and correlation between individual and panel reviews were strong. Clinical benefit scores showed good concordance with the protocol-specified ORR obtained by an independent review facility and with investigator-assessed response.

Conclusion.

Clinical benefit assessed by independent review based on expert clinical judgment provides strong evidence that treatment with vismodegib results in clinically meaningful and durable responses in patients with laBCC.     

Diagnosis and Therapy of Primary Hepatic Neuroendocrine Carcinoma: Clinical Analysis of 10 Cases

Background: Primary hepatic neuroendocrine carcinoma (PHNEC) is rarer than extrahepatic gastrointestinalneuroendocrine carcinoma (NEC). It is difficult to make a correct diagnosis and poses a challenge for management.Materials and Methods: Ten PHNEC patients were admitted to our hospital from June 2006 to June 2011.Laboratory tests and imaging scans were performed for diagnosis and exclusion of extrahepatic NEC. All patientswere AFP - and CA199- . Seven patients had solid tumors with cystic changes on ultrasonography, CT and/orMRI. For the initial treatment, four patients received combined-therapy and six monotherapy. Consideringoverall treatment, six patients received combined-therapy and four patients monotherapy. Staging criteria ofprimary hepatocellular carcinoma (PHC, AJCC 7th edition) were used to differentiate the stage of all patients:3 patients were stage Ⅰ, 2 stageⅡ, 4 patients stageⅢ and 1 stageⅣ. All patients were followed up and clinicaldata were gathered. Results: The median follow-up duration was 38.5 months. The 1-year, 2-year, 3-year and6-year disease-free survival was 80.0%, 46.2% and 46.2% and 0% respectively. The overall survival rates were100%, 67.1%, 67.1% and 33.6% respectively. Patients in early-stages (Ⅰ/Ⅱ) had similar disease-free and overallsurvival as those in advanced-stages (Ⅲ/Ⅳ). Patients with monotherapy had significant shorter disease-freeand overall survival than the patients with combination-therapy. Conclusions: PHNEC has a unique specificityduring its occurrence and development. The staging criteria of PHC might not be suitable for the PHENT. Moreconvenient and effective features need to be found in imaging and laboratory detection. Surgical resection, TACE,chemotherapy and radiofrequency ablation should be performed in combination and actively for patients withPHNEC or recurrence to get the best effectiveness; they might extend the disease-free and overall survival.     

The Role of Systemic Therapy in the Management of Stage I Large Cell Neuroendocrine Carcinoma of the Lung

Introduction

The optimal treatment strategy for resected stage I large cell neuroendocrine carcinoma of the lung (LCNEC) remains unknown. In this analysis, we evaluate the impact of systemic chemotherapy on patients with stage I LCNEC who have undergone surgical resection.

胰腺癌临床研究进展

本文阐述了近年来国内外关于胰腺癌的病因，诊断和治疗等方面的研究进展，探索胰腺癌诊断和治疗的有效方式。尽管胰腺癌的诊断和治疗取得了很大进展。尚需继续研究改进治疗方法，延长患者的生存期。     

Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

IntroductionRecent classification of neuroendocrine neoplasms has defined well‐differentiated high‐grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well‐described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.Materials and MethodsThis was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients’ demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression‐free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).ResultsTreatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki‐67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum‐etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96–16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.ConclusionAmong patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short‐lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.Implications for PracticeHigh‐grade well‐differentiated neuroendocrine tumors (NET G3) are considered a different entity from low‐grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well‐differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.     

Prolonged Survival in a Patient with a Pancreatic Acinar Cell Carcinoma

Pancreatic acinar cell carcinoma (ACC) is a rare entity. Herein we present the case of a 50-year-old male patient with an unlimited mass on the pancreatic corpus and tail with peripancreatic effusion and multiple metastases in the liver and spleen. A liver biopsy showed a pancreatic ACC. The patient received 9 cycles of gemcitabine plus oxaliplatin (GEMOX regimen), which had to be stopped because of a persistent grade 2 neuropathy. A CT scan showed complete response after 14 years. At the age of 61 years, a localized prostatic cancer was diagnosed, treated by prostatectomy. The patient carried a BRCA2 mutation. None of the precedent case reports describe a chemosensibility to the GEMOX regimen. In spite of the lack of study in these patients, chemotherapy with oxaliplatin seems to be the most effective. Long survival can be expected.Key Words: Pancreatic acinar cell carcinoma, Long-term survival, BRCA2 mutation