Use of [177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study

AimTo evaluate the cost-effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs).Materials and methodsA three-state partitioned survival model was developed to perform a cost-utility analysis of [¹⁷⁷Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan–Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [¹⁷⁷Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [¹⁷⁷Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case).ResultsIn GI-NETs, the incremental cost-effectiveness ratio (ICER) of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively.ConclusionsAt a willingness to pay threshold of £30,000, [¹⁷⁷Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).     

Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

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Next generation immunohistochemistry: Emerging substitutes to genetic testing?

The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).     

Giant insulinoma in a 15-year-old man: A case report

IntroductionGiant insulinomas are extremely rare pancreatic neuroendocrine tumor.Presentation of caseA 15-year-old man presenting with acute onset of lightheadedness was found to have serum glucose of 1.5 mmol/L. The blood collected from the hypoglycemic episode showed an inappropriately high insulin and C-peptide level. Abdominal computerized tomography showed a 12.5 cm well-defined, lobulated hypervascular mass at pancreatic tail, without any evidence of metastasis. En bloc resection with distal pancreatectomy, and splenectomy was successfully performed. The pathological examination confirmed insulinoma, with benign characteristics. Follow-up after the procedure revealed neither hypoglycemic, nor hyperglycemia.ConclusionWe report the youngest case of a giant insulinoma. Despite the size of the tumor, the pathological report confirmed the benign characteristics. However, long-term follow-up is still essential to detect recurrence in the future.     

胃肠道神经内分泌肿瘤预后的影响因素及干预对策

目的探讨影响胃肠道神经内分泌肿瘤预后的因素,并提出相应干预对策,以期能够改善患者预后。方法选择2005-03—2012-03我院收治的胃肠道神经内分泌肿瘤患者54例,对患者的临床资料及随访情况进行回顾性分析,首先采用Kaplan-Meier法进行单因素分析,多因素分析采用Cox回归分析。结果本组54例患者均获随访,患者的中位生存期为27个月,单因素分析结果显示,年龄、淋巴转移、远处转移以及肿瘤大小4个因素差异具有统计学意义（P〈0.05）;多因素分析结果显示,年龄及淋巴转移进入Cox回归模型（P〈0.05）。结论影响胃肠道神经内分泌肿瘤患者预后的因素包括年龄、淋巴转移、远处转移以及肿瘤大小,特别对于年龄60周岁以上以及淋巴转移是患者预后差的独立指标。     

腹腔镜同期手术治疗胃神经内分泌癌肝转移1例

胃神经内分泌癌（Gastric neuroendocrine carcinoma，G-NEC）是一类少见的起源于胃神经内分泌细胞的高度恶性肿瘤。GB-NEC 侵袭性强，易于发生淋巴结和远处转移，预后较差。肝脏是G-NEC 最常见的远处转移部位。目前，对于G-NEC 伴肝脏转移的治疗仍存在争议，尚无腹腔镜手术治疗G-NEC 伴肝转移的相关报道。在这里，本文回顾性分析了1 例G-NEC 伴肝转移患者的临床特点和诊治经过。患者因“恶心伴食欲不振3 个月”入院，结合病史、体格检查及辅助检查结果，术前考虑诊断为胃恶性肿瘤伴肝转移，接受了腹腔镜胃癌根治术（全胃切除+食道空肠Roux-en-Y 吻合+D2 淋巴结清扫）+左肝外叶切除+空肠造瘘术，术后无严重并发症发生并顺利出院。术后予以6 个周期的“依托泊苷+顺铂”方案化疗，随访患者术后2 年未见肿瘤复发。