Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial.

BACKGROUND: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. METHODS: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. RESULTS: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). CONCLUSIONS: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients.

BACKGROUND: Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment. METHODS: This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments. Detected alterations were described according to ESMO Scale of Clinical Actionability for molecular Targets (ESCAT). RESULTS: NGS analysis was performed in 68 patients affected by PDC. At least one alteration ranking tier I, II, III, or IV according to ESCAT classification was detected in 8, 1, 9, and 12 patients respectively (44.1%). Ten of them (33.3%) received a matched therapy. Patients with ESCAT tier I to IV were generally younger than the overall population (median = 54, range = 26-71 years), had an EGOG performance status score = 0 (83.3%), and an uncommon histological or clinical presentation. The most common mutations with clinical evidence of actionability (ESCAT tier I-III) involved genes of the RAF (10.3%), BRCA (5.9%) or FGFR pathways (5.9%). We present the activity of the RAF kinases inhibitor sorafenib in patients with RAF-mutated advanced PDC. CONCLUSIONS: In advanced PDC, NGS is a feasible and valuable method for enabling precision oncology. This genomic profiling method might be considered after standard treatments failure, especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches.

Percutaneous ablation of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review.

Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma.

BACKGROUND: To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. METHODS: In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. RESULTS: In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than 30% reduction of CA 19.9 levels. CONCLUSIONS: RFA of unresectable pancreatic adenocarcinoma induces reduction of CA 19.9 blood levels in about half of the cases.

Ultrasound-guided percutaneous fine-needle aspiration of solid pancreatic neoplasms: 10-year experience with more than 2,000 cases and a review of the literature.

OBJECTIVES: To evaluate the diagnostic accuracy and complication rate of percutaneous ultrasound-guided fine-needle aspiration (US-FNA) of solid pancreatic neoplasms through the analysis of 10-year experiences of two centres. METHODS: Clinical, radiological and pathologic data of 2,024 patients with solid pancreatic masses who underwent US-FNAs were retrospectively evaluated. Indications for aspiration were: unresectable lesions before neo-adjuvant therapy; doubtful imaging findings; and suspicion of uncommon neoplasms with prognostic or therapeutic implications such as metastases or lymphoma. US-FNAs were performed using aspiration needles with a cytopathologist present in centre 1. In centre 2, cytologic samples were collected with Chiba needles and separately evaluated by a cytopathologist. RESULTS: US-FNA had a diagnostic sample rate of 92.2 % (centre 1: 95.9 %; centre 2: 87.2 %). US-FNA repetition after non-diagnostic samples provided a diagnosis in 86.3 % of cases. Sensitivity, specificity, positive and negative predictive values, and accuracy were 98.7 %, 100 %, 100 %, 75.5 %, and 98.7 %, respectively. The complication rate was 0.8 %. CONCLUSIONS: Percutaneous US-FNA is a sensitive, accurate and safe method for the invasive diagnosis of solid pancreatic neoplasms. The use of aspiration needles and the on-site presence of a cytopathologist may lead to a high rate of diagnostic samples, thus reducing the need for US-FNA repetition. KEY POINTS: • Percutaneous ultrasound-guided fine-needle aspiration of pancreatic neoplasms is sensitive and accurate. • The short-term complication rate of percutaneous ultrasound-guided fine-needle aspiration is low. • Technical aspects may influence the rate of diagnostic samples.

Uncommon presentations of common pancreatic neoplasms: a pictorial essay.

Pancreatic neoplasms are a wide group of solid and cystic lesions with different and often characteristic imaging features, clinical presentations, and management. Among solid tumors, ductal adenocarcinoma is the most common: it arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms, and generally has a bad prognosis; its therapeutic management must be multidisciplinary, involving surgeons, oncologists, gastroenterologists, radiologists, and radiotherapists. The second most common solid pancreatic neoplasms are neuroendocrine tumors: they can be divided into functioning or non-functioning and present different degrees of malignancy. Cystic pancreatic neoplasms comprise serous neoplasms, which are almost always benign, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are rarely seen in clinical practice and have different and sometimes controversial managements. Rare clinical presentations and imaging appearance of the most common pancreatic neoplasms, both solid and cystic, are more frequently seen and clinically relevant than rare pancreatic tumors; their pathologic and radiologic appearances must be known to improve their management. The purpose of this paper is to present some rare or uncommon clinical and radiological presentations of common pancreatic neoplasms providing examples of multi-modality imaging approach with pathologic correlations, thus describing the histopathological bases that can explain the peculiar imaging features, in order to avoid relevant misdiagnosis and to improve lesion management.

Contrast-enhanced ultrasound of pancreatic tumours.

Indication/purpose: To review contrast-enhanced ultrasound features of the most common pancreatic tumours. Methods: Contrast-enhanced ultrasound (CEUS) can provide distinctive features of pancreatic tumours that are reported in the present paper, providing radiologic-pathological correlations and clarifying the main differential diagnosis. Conclusion: Contrast-enhanced ultrasound plays a well-established role in the evaluation of pancreatic tumours. When possible, CEUS should be always performed after the initial US diagnosis, in order to improve the accuracy of the first line examination.

Pancreatic multicenter ultrasound study (PAMUS).

AIM: To describe the typical CEUS pattern of pancreatic lesions and to evaluate the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) in their characterization. MATERIALS AND METHODS: All US and CEUS examinations of focal pancreatic masses performed in six centers during a period of five years were reviewed. Inclusion criteria were: focal pancreatic mass pathologically proved, visible at ultrasound (US) and studied with CEUS. All lesions were then evaluated for size, aspect and enhancement pattern. Sensitivity, specificity, positive and negative predictive values with 95% CIs were calculated to define diagnostic accuracy of CEUS in respect to pathology. Diagnostic confidence of US and CEUS, discerning between benign and malignant lesions, were represented by using ROC (receiver operating characteristics) curves. Agreement was evaluated by means of k statistics. RESULTS: 1439 pancreatic lesions were included. At CEUS the lesions were divided into solid (89%) and cystic (12%) masses and classified into six and eight categories, respectively. Among the solid lesions, adenocarcinomas were characterized with an accuracy of 87.8%. Among the cystic lesions, cystic tumors were diagnosed with an accuracy of 97.1%. ROC curve area increased from 0.637 for US to 0.877 for CEUS (p<0.0001). Inter-observer agreement was slightly higher for solid (k=0.78) than cystic (k=0.62) lesions. In none of the centers side effects were reported. CONCLUSION: CEUS is accurate in the characterization of pancreatic lesions. CEUS should be considered as a complementary imaging method for pancreatic lesions characterization.

Radiofrequency ablation of locally advanced pancreatic adenocarcinoma: an overview.

Radiofrequency ablation (RFA) of pancreatic neoplasms is restricted to locally advanced, non-resectable but non-metastatic tumors. RFA of pancreatic tumors is nowadays an ultrasound-guided procedure performed during laparotomy in open surgery. Intraoperative ultrasound covers the mandatory role of staging, evaluation of feasibility, guidance and monitoring of the procedure. Different types of needle can be used. The first aim in the evaluation of RFA as a treatment for locally advanced pancreatic ductal adenocarcinoma, in order of evaluation but not of importance, is to determine the feasibility of the procedure. The second aim is to establish the effect of RFA on tumoral mass in terms of necrosis and cytoreduction. The most important aim, third in order of evaluation, is the potential improvement of quality of life and survival rate. Nowadays, only a few studies assess the feasibility of the procedure. The present paper is an overview of RFA for pancreatic adenocarcinoma.