Current Challenges in Diagnosis and Assessment of the Response of Locally Advanced and Metastatic Renal Cell Carcinoma.

Locally advanced and metastatic renal cell carcinoma (RCC) present a specific set of challenges to the radiologist. The detection of metastatic disease is confounded by the ability of RCC to metastasize to virtually any part of the human body long after surgical resection of the primary tumor. This includes sites not commonly included in routine surveillance, which come to light after the patient becomes symptomatic. In the assessment of treatment response, the phenomenon of tumor heterogeneity, where clone selection through systemic therapy drives the growth of potentially more aggressive phenotypes, can result in oligoprogression despite overall disease control. Finally, advances in therapy have resulted in the development of immuno-oncologic agents that may result in changes that are not adequately evaluated with conventional size-based response criteria and may even be misinterpreted as progression. This article reviews the common challenges a radiologist may encounter in the evaluation of patients with locally advanced and metastatic RCC. ©RSNA, 2019.

[Usefulness of endoscopic ultrasound guided elastography in the assessment of solid pancreatic lesions]. / Utilidad de la elastografía guiada por ultrasonografía endoscópica en la evaluación de lesiones sólidas pancreáticas.

INTRODUCTION: endoscopic ultrasonography (EUS) elastography is considered a useful tool for the evaluation of solid pancreatic lesions (SPL). OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of elastography in patients with SPL. MATERIAL AND METHODS: A prospective, cross-sectional study was performed at the Rebagliati Hospital between July 2017 and June 2018. Patients with a diagnosis of SPL and echoendoscopic study, elastography and FNA were included. Qualitative and quantitative elastography: strain ratio (SR) and strain histogram, were performed and analyzed with histopathological results. The diagnostic accuracy of EUS elastography in detecting malignancy was calculated using receiver operating curve analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the detection of malignancy were calculated. RESULTS: Out of 832 EUS examinations performed, 46 patients with SPL (mean age, 64.6 years; 29 women) were included in the study. Pancreatic adenocarcinoma was diagnosed in 36 cases. In qualitative elastography, score 3 was most frequent (n = 39, 84.8%) with sensitivity, specificity and accuracy of 88.9%, 30% and 76.1%, respectively, for predict adenocarcinoma. A strain ratio of 15 or higher (100% sensitivity, 66.7% specificity and 97.8% accuracy) and a histogram of less than 49 (66.7% sensitivity, 97.6% specificity and 95.6% accuracy) predicts malignancy in SPL, with area under a ROC curve of 0.941 (95% CI, 0.82 - 1.0). CONCLUSIONS: EUS elastography provides information to predict the malignant nature of the pancreatic lesion. In our study, the elastographic detection of a score 3, SR≥15 or a histogram <49 predicts the presence of malignancy in LSP.

Utilidad de la elastografía guiada por ultrasonografía endoscópica en la evaluación de lesiones sólidas pancreáticas / Usefulness of endoscopic ultrasound guided elastography in the assessment of solid pancreatic lesions

Introducción: La elastografía guiada por ultrasonografía endoscópica es considerada una herramienta útil en la evaluación de las lesiones solidas pancreáticas (LSP). Objetivo: El objetivo del estudio fue evaluar el rendimiento diagnóstico de la elastografia en pacientes con LSP. Material y métodos: Se realizó un estudio transversal prospectivo en el hospital Rebagliati durante julio 2017 a junio 2018. Se incluyeron pacientes con diagnóstico de LSP y estudio ecoendoscópico, elastografía y toma de PAAF. Se realizó elastografia cualitativa y elastografia cuantitativa (SR e histograma) y se analizó con resultados histopatológicos para determinar la sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN) y exactitud diagnostica en la detección de malignidad. Resultados: De 846 ecoendoscopías, se estudiaron 46 pacientes con LSP con una edad promedio de 64,6 años, 29 (63%) sexo femenino. El adenocarcinoma pancreático fue diagnosticado en 36 casos (78,3%). En elastografía cualitativa predominó el score 3 (n=39, 84,8%) con una sensibilidad, especificidad y exactitud de 88.9%, 30% y 76,1% respectivamente para predecir adenocarcinoma. Elastografía cuantitativa de SR≥ 15 (sensibilidad 100%, especificidad 66,7% y exactitud 97,8%) y un valor de histograma menor de 49 (sensibilidad 66,7%, especificidad 97,6% y exactitud 95,6%) predice malignidad en una LSP con área bajo de la curva ROC de 0,941 (IC 95%, 0,82 - 1,0). Conclusiones: La elastografía brinda información para predecir la naturaleza maligna de la lesión. En nuestro estudio la detección elastográfica de un score 3, SR≥ 15 o un histograma < 49 predice la presencia de malignidad en la LSP estudiada.

Introduction: endoscopic ultrasonography (EUS) elastography is considered a useful tool for the evaluation of solid pancreatic lesions (SPL). Objective: The aim of our study was to evaluate the diagnostic performance of elastography in patients with SPL. Material and methods: A prospective, cross-sectional study was performed at the Rebagliati Hospital between July 2017 and June 2018. Patients with a diagnosis of SPL and echoendoscopic study, elastography and FNA were included. Qualitative and quantitative elastography: strain ratio (SR) and strain histogram, were performed and analyzed with histopathological results. The diagnostic accuracy of EUS elastography in detecting malignancy was calculated using receiver operating curve analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the detection of malignancy were calculated. Results: Out of 832 EUS examinations performed, 46 patients with SPL (mean age, 64.6 years; 29 women) were included in the study. Pancreatic adenocarcinoma was diagnosed in 36 cases. In qualitative elastography, score 3 was most frequent (n = 39, 84.8%) with sensitivity, specificity and accuracy of 88.9%, 30% and 76.1%, respectively, for predict adenocarcinoma. A strain ratio of 15 or higher (100% sensitivity, 66.7% specificity and 97.8% accuracy) and a histogram of less than 49 (66.7% sensitivity, 97.6% specificity and 95.6% accuracy) predicts malignancy in SPL, with area under a ROC curve of 0.941 (95% CI, 0.82 - 1.0). Conclusions: EUS elastography provides information to predict the malignant nature of the pancreatic lesion. In our study, the elastographic detection of a score 3, SR≥15 or a histogram <49 predicts the presence of malignancy in LSP.

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA. OBJECTIVE: The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA. METHODS: A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used. RESULTS: FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis. CONCLUSIONS: This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year.

Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000-£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

Cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors: true incidence and management.

BACKGROUND: The incidence, clinical importance, and optimal management of cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors (NETS) are largely unknown. Historically, cervical nodes have been regarded as asymptomatic and ignored. We hypothesized that these lesions have clinical implications and should be removed surgically. STUDY DESIGN: Consecutive (111)In pentetreotide scans (OctreoScan) performed at our institution from May 2008 to October 2010 were reviewed to determine the incidence of cervical and upper mediastinal lymph node metastases among patients with gastrointestinal and pancreatic NETs. The charts of surgically treated patients were reviewed to evaluate the clinical importance of these metastases and the subsequent outcomes of their surgical treatment. RESULTS: A total of 161 NET patients presented with positive OctreoScans. Fourteen patients (8.7%) scanned positive for cervical and upper mediastinal lymph node metastasis. Nine patients underwent surgical exploration; 8 had successful removal of their metastatic nodes. Seven had clinical symptoms that resolved after surgery. CONCLUSIONS: Cervical and upper mediastinal lymph node metastases from gastrointestinal and pancreatic NETs were seen in up to 8.7% of patients. In the past, these metastases were assumed to be insignificant and ignored. Our study clearly demonstrates that most, if not all, such metastases are symptomatic and their clinical implications should not be overlooked. Notably, these metastases can be easily and safely resected using radioguided surgery.

[Diagnosis and assessment of pancreatic cancer]. / Diagnostik og udredning af cancer pancreatis.

A precise, lenient and multidisciplinary pre-therapeutic evaluation is mandatory in order to reach an optimal treatment decision in patients with pancreatic cancer. Endoscopic ultrasonography (EUS), computed tomography, laparoscopy and laparoscopic ultrasonography (LAP/LUS) are used in the diagnosis, TNM-staging and resectability assessment of these patients. Ductal adenocarcinoma is the most common tumour of the pancreas, and biopsies may be obtained during transabdominal ultrasound, EUS or LUS. However, preoperative confirmation of malignancy is not necessary unless chemo- or chemoradiation therapy is indicated.

Budget impact model of adding erlotinib to a regimen of gemcitabine for the treatment of locally advanced, nonresectable or metastatic pancreatic cancer.

OBJECTIVE: The aim of this study was to determine the budget impact of adding erlotinib to a US health plan insurer's formulary as a combination therapy with gemcitabine for the treatment of nonresectable pancreatic cancer. METHODS: An Excel-based budget impact model was developed to evaluate the costs for National Comprehensive Cancer Network guideline-recommended treatment options for patients with locally advanced, nonresectable or metastatic pancreatic cancer from the perspective of a US managed care plan. The model compared treatment with gemcitabine alone and in combination with erlotinib, including the costs of treatment, adverse events (AEs), and administration. Inputs for the model were derived from the Surveillance, Epidemiology and End Results Cancer Registry, clinical trials, and publicly available sources and were varied in sensitivity analyses to identify influential inputs. The model addressed first-line use in a single indication and assumed that the proportion of patients aged >or=65 years in a managed care organization was the same as in the general population. The model did not account for patient copayments for oral medications, a factor that could lower a plan's overall cost further than estimated herein. RESULTS: For a hypothetical managed care plan with 500,000 members, the model estimated 43 newly diagnosed pancreatic cancer cases each year, of which 56% (n=24) would be treated with gemcitabine as first-line therapy. Assuming that erlotinib were added to the treatment regimen in 40% (n=10) of gemcitabine-treated patients for 15.7 weeks of therapy per patient, the expected 1-year cost in 2006 dollars would be US $466,700 compared with $346,700 had all patients been treated with gemcitabine alone. Administration costs accounted for 10% to 12% of total costs, while AE management costs made up 14% to 16% of total costs. These estimates corresponded to an incremental cost of $120,000, or $0.020 per member per month (PMPM). The results were relatively insensitive to drug costs, drug administration costs, and costs of treatment of AEs based on sensitivity analyses. CONCLUSIONS: In this analysis of the budget impact of adding to the health plan formulary erlotinib to a regimen of gemcitabine as first-line treatment of locally advanced, nonresectable or metastatic pancreatic cancer in the United States, the budget impact was $0.020 PMPM. The relatively low incidence of pancreatic cancer and the assumption of treating only 23% of these patients with erlotinib were likely the principal reasons for the low budgetary impact of erlotinib. In this model and using these reasonable assumptions, the results suggested that the incremental cost impact on a PMPM basis may be small.

Osteoblastic flare in a patient with advanced gastric cancer after treatment with pemetrexed and oxaliplatin: implications for response assessment with RECIST criteria.

BACKGROUND: The RECIST guidelines are commonly used in phase II and III clinical trials. The correct definition of response can be controversial in some situations, as in the case we describe. CASE PRESENTATION: A 43 year-old man with advanced gastric cancer was enrolled in a phase II trial where he was treated with pemetrexed 500 mg/m2 plus oxaliplatin 120 mg/m2 every 3 weeks. At baseline, the target lesions were lymph-nodes, and the non-target lesions were small pulmonary nodules. At first re-evaluation, the target lesions showed partial response and the non-target lesions showed complete response, but new diffuse osteoblastic lesions appeared. The investigator decided to continue treatment until the second re-evaluation. CT scan confirmed the response of the target and non-target lesions, while the osteoblastic lesions did not change. CONCLUSION: The appearance of osteoblastic lesions after an active antitumor treatment, a phenomenon known as flare, can complicate the definition of the best overall response using RECIST criteria. This possibility should be considered by oncologists involved in clinical trials.

Preoperative assessment of advanced gastric carcinoma using computed tomography.

OBJECTIVES: The role of computed tomography (CT) for the staging of gastric carcinoma is controversial. The purpose of this study was to evaluate the utility of CT in assessing the perigastric spread of advanced gastric carcinoma. METHODS: The study included 56 patients who underwent dynamic CT and laparotomy for the treatment of node-positive gastric adenocarcinoma. Preoperative CT findings were compared with surgical findings, and diagnostic accuracy was estimated. RESULTS: Sensitivity, specificity, and accuracy of preoperative CT in determining the perigastric tumor spreads were 33, 97, and 73% in pancreatic invasion, 36, 97, and 70% in level III lymph node involvement, and 89, 98, and 96% in liver metastasis. Peritoneal dissemination was not detected in 15 of 56 patients (27%), and stage IV disease was not diagnosed correctly in 18 of 40 patients (45%). CONCLUSIONS: Radiologists and surgeons must remember that pancreatic invasion, extended lymph node metastasis, and peritoneal dissemination are sometimes overlooked in CT examination in patients with advanced gastric carcinoma.

Pancreatic metastases: CT assessment.

We report the CT appearance of pancreatic metastases and describe their features in relation to the originating primary tumor. We also discuss some limitations in their differential diagnosis and report some theories explaining the pathogenesis of their occurrence. A total of 20 cases (9 males and 11 females) of pancreatic metastases were diagnosed at staging or follow-up of oncologic patients. All patients were evaluated with CT before and after contrast medium administration and had subsequent pathologic confirmation. In 1 case metastases were located solely in the pancreas; in 6 there was only another metastatic location, and in the remaining 13 there was diffuse spread throughout the body. Two of our patients exhibited a multinodular metastatic involvement of the pancreas, 11 had a solitary nodule or mass, and the remaining 7 had a diffusely enlarged pancreas, without any signs of focal disease. All but one of the solitary lesions measured more than 4 cm. In 2 cases a metachronous malignancy was detected at follow-up. Primary malignancies were located: 6 in the lungs, 2 on the skin (melanomas), 3 in breasts, 2 in the ovaries, 3 in the colon, 1 in the stomach, 2 in the kidney, and 1 the thyroid. Our findings confirm the existence of three patterns of metastatization to the pancreas: large solitary masses, multinodular lesions, and diffuse enlargement of the pancreas without focal signs at CT. In contrast to other studies, the large solitary lesion was our most frequent encounter, therefore making differential diagnosis vs primary cancer difficult. Metastases tended to repeat the imaging pattern of the primary. Nevertheless, we wrongly diagnosed pancreatitis due to a small nondetected metastasis, pseudo-cystic mass as a mucinous cystadenocarcinoma, conglomerate of peripancreatic lymph nodes, and a solitary pancreatic mass diagnosed as primary pancreatic cancer. Thus, when faced with a solitary pancreatic lesion at follow-up, histologic diagnosis is strongly recommended. In 2 cases changes in aspect and size were related to therapy.