Motoyo Yano

Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial

BACKGROUND In pancreatic ductal adenocarcinoma, the CCL2-CCR2 chemokine axis is used to recruit tumour-associated macrophages for construction of an immunosuppressive tumour microenvironment. This pathway has prognostic implications in pancreatic cancer, and blockade of CCR2 restores anti-tumour immunity in preclinical models. We aimed to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX chemotherapy (oxaliplatin and irinotecan plus leucovorin and fluorouracil). METHODS We did this open-label, dose-finding, non-randomised, phase 1b study at one centre in the USA. We enrolled treatment-naive patients aged 18 years or older with borderline resectable or locally advanced biopsy-proven pancreatic ductal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1, and normal end-organ function. Patients were allocated to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), and bolus fluorouracil 400 mg/m(2), followed by 2400 mg/m(2) 46-h continuous infusion), administered every 2 weeks for a total of six treatment cycles, or in combination with oral PF-04136309, administered at a starting dose of 500 mg twice daily in a standard 3 + 3 dose de-escalation design. Both FOLFIRINOX and PF-04136309 were simultaneously initiated with a total treatment duration of 12 weeks. The primary endpoints were the safety, tolerability, and recommended phase 2 dose of PF-04136309 plus FOLFIRINOX, with an expansion phase planned at the recommended dose. We analysed the primary outcome by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01413022. RESULTS Between April 19, 2012, and Nov 12, 2014, we treated 47 patients with FOLFIRINOX alone (n=8) or with FOLFIRINOX plus PF-04136309 (n=39). One patient had a dose-limiting toxic effect in the dose de-escalation group receiving FOLFIRINOX plus PF-04136309 at 500 mg twice daily (n=6); this dose was established as the recommended phase 2 dose. We pooled patients in the expansion-phase group (n=33) with those in the dose de-escalation group that received PF-04136309 at the recommended phase 2 dose for assessment of treatment-related toxicity. Six (75%) of the eight patients receiving FOLFIRINOX alone were assessed for treatment toxicity, after exclusion of two (25%) patients due to insurance coverage issues. The median duration of follow-up for treatment toxicity was 72·0 days (IQR 49·5-89·0) in the FOLFIRINOX alone group and 77·0 days (70·0-90·5) in the FOLFIRINOX plus PF-04136309 group. No treatment-related deaths occurred. Two (5%) patients in the FOLFIRINOX plus PF-04136309 group stopped treatment earlier than planned due to treatment-related toxic effects. Grade 3 or higher adverse events reported in at least 10% of the patients receiving PF-04136309 included neutropenia (n=27), febrile neutropenia (n=7), lymphopenia (n=4), diarrhoea (n=6), and hypokalaemia (n=7). Grade 3 or higher adverse events reported in at least 10% of patients receiving FOLFIRINOX alone were neutropenia (n=6), febrile neutropenia (n=1), anaemia (n=2), lymphopenia (n=1), diarrhoea (n=2), hypoalbuminaemia (n=1), and hypokalaemia (n=3). Therapy was terminated because of treatment-related toxicity in one (17%) of the six patients receiving FOLFIRINOX alone. 16 (49%) of 33 patients receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective tumour response, with local tumour control achieved in 32 (97%) patients. In the FOLFIRINOX alone group, none of the five patients with repeat imaging achieved an objective response, although four (80%) of those patients achieved stable disease. INTERPRETATION CCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable. FUNDING Washington University-Pfizer Biomedical Collaborative.

MR Imaging Findings of Ectopic Pregnancy: A Pictorial Review

Because of its lack of ionizing radiation and excellent soft-tissue contrast, magnetic resonance (MR) imaging is being increasingly used in the evaluation of acute abdominal pain in the pregnant patient. Roughly 2% of all pregnancies are ectopic. Although ectopic pregnancy is usually diagnosed on the basis of a combination of clinical, laboratory, and ultrasonographic findings, it occasionally is initially identified at MR imaging. Thus, it is imperative that the radiologist should be familiar with the variable appearance of ectopic pregnancy at MR imaging and should evaluate for ectopic pregnancy at any time when (a) a patient has positive results of a pregnancy test and (b) an intrauterine pregnancy is not definitively seen. Because of potential issues of fetal safety, a conservative approach should be used for MR imaging in pregnancy. An MR imaging protocol for the evaluation of possible appendicitis in pregnant women is detailed. Specific findings that can aid in the diagnosis of ectopic pregnancy are the lack of an intrauterine pregnancy, isolated hemoperitoneum, tubal masses, hematosalpinx, and interstitial masses. In the differential diagnosis of acute abdominal pain in pregnancy, consideration should be given to the more unusual forms of ectopic pregnancy, such as angular pregnancy, cornual pregnancy, and abdominal pregnancy. Potential mimics of ectopic pregnancy include placental abnormalities, ovarian neoplasms, and corpus luteum cysts.

Induction Chemotherapy Followed by Concurrent Full-dose Gemcitabine and Intensity-modulated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.

Objective:To evaluate the outcomes and toxicity of concurrent full-dose gemcitabine and intensity-modulated radiation therapy (IMRT) for patients with borderline resectable and locally advanced pancreatic adenocarcinoma after induction chemotherapy. Materials and Methods:From 2009 to 2012, 32 patients were treated with concurrent gemcitabine and IMRT for borderline resectable or locally advanced pancreatic adenocarcinoma. All patients received induction FOLFIRINOX or gemcitabine-based chemotherapy before chemoradiation. The radiotherapy volume was limited to the primary tumor, and the median dose was 55 Gy in 25 fractions. Gemcitabine was administered weekly during radiotherapy on days 1, 8, 22, and 29 at a median weekly dose of 800 mg/m2. Results:Twenty-five patients had locally advanced disease and 7 had borderline resectable disease. The median follow-up time was 14.6 months. The median progression-free and overall survival were 13.9 and 23.1 months, with a trend toward improved overall survival for patients receiving induction FOLFIRINOX compared with gemcitabine-based therapy. A radiographic complete or partial response was achieved in 13 patients (41%), with 4 (13%) having complete radiographic responses. Surgical resection was performed in 10 patients (31%)—6 patients with locally advanced disease and 4 with borderline resectable disease. Grade 3/4 hematologic toxicity during and up to 6 weeks after chemoradiation occurred in 12 patients (38%); grade 3 nonhematologic toxicity occurred in 7 patients (22%), with no grade 4 or 5 toxicity. All patients completed their radiotherapy. Conclusions:Concurrent full-dose gemcitabine and limited-field IMRT after induction chemotherapy for the treatment of borderline resectable and locally advanced pancreatic cancer is promising with acceptable toxicity rates.

MRI of the stomach: a pictorial review with a focus on oncological applications and gastric motility

Abstract The purpose of this pictorial review is to demonstrate gastric pathology seen on magnetic resonance imaging (MRI) and discuss the essential MRI sequences for the evaluation of benign and malignant gastric pathologies. Common tumors of the stomach, polyposis syndromes, iatrogenic conditions, as well as other conditions of the stomach will be reviewed. The utility of MRI in the evaluation of patients with gastric malignancies and disorders of gastric motility will also be discussed.

Hot spleen: hypervascular lesions of the spleen

AbstractThe differential diagnosis of splenic masses is broad and often hinges on the enhancement characteristics of the lesions. Most radiologists are familiar with the differential diagnosis of hypovascular lesions such as fungal infections, sarcoidosis/granulomatous disease, infarctions, and cysts. However, to our knowledge, there is no review article that presents the specific multimodality imaging features of vascular splenic lesions as a group. Vascular splenic lesions may be considered those that enhance more or similarly to the background splenic parenchyma. In this review, we illustrate the spectrum of imaging features of both benign and malignant vascular splenic lesions. The benign lesions include hemangiomas, hamartomas, and sclerosing angiomatoid nodular transformation of the spleen. The malignant lesions are divided into primary and metastatic lesions, ranging from lymphoma, angiosarcoma to pleomorphic sarcoma. While lymphoma and metastases may commonly present as hypoenhancing lesions relative to the background parenchyma, we are addressing them here as their appearance can be varied and hence deserve consideration. Littoral Cell angiomas are discussed separately, as they were originally considered benign, but recent studies have shown that they can have malignant potential.

Magnetic resonance imaging of iatrogeny: understanding imaging artifacts related to medical devices

Medical devices are frequently encountered in patients presenting for imaging studies. Knowledge of the device composition, dwell time, and location is essential for determining the safety and potential impact on the quality of magnetic resonance imaging (MRI) examinations. Anticipation of MRI artifacts associated with implanted devices allows the radiologist to adjust parameters to mitigate their effect on the anatomy of interest and to avoid pitfalls in interpretation. The purpose of this article is to present a pictorial review of the MRI appearance of commonly encountered implanted devices and foreign objects in order to help the radiologist anticipate their impact on final image quality.

Direct puncture sclerotherapy of a thoracic duct cyst presenting as an enlarging left supraclavicular mass

A 58-year-old woman presented with a palpable mass at the base of the left neck which she had first noticed 12 years previously, shortly after abdominal surgery. The mass had progressively enlarged, resulting in dysphagia, dyspnea and occasional pain. Imaging showed a septated but otherwise simple cystic mass extending into the mediastinum and containing lymphocytic fluid on aspiration. A diagnosis of the rare entity of a thoracic duct cyst with supraclavicular extension was made. The patient opted for percutaneous sclerotherapy of the lesion, which was performed using glacial acetic acid. This resulted in complete resolution of the mass with one treatment. After exclusion of other causes of cystic left supraclavicular masses including cystic neoplasms and pseudoaneurysms of the carotid or subclavian arteries, direct puncture sclerotherapy can be safe and effective.

Assessment of disease aggression in cystic pancreatic neuroendocrine tumors: A CT and pathology correlation study

BACKGROUND/OBJECTIVES There are inconsistencies in the literature regarding the clinical significance of cystic components in pancreatic neuroendocrine tumors (NET). This may be related to differences in the identification of cystic NET through imaging and/or pathology. Tumors may also be microscopically or macroscopically cystic. Our primary objective is to determine radiology-pathology correlation for the identification of cystic components. Our secondary objective is to determine if cystic components are associated with indices of tumor aggression. METHODS 60 tumors with correlative surgical pathology were assessed retrospectively for cystic components on CT and pathology. Tumor was categorized as solid or cystic on CT and pathology. If cystic on pathology, cystic components were categorized as macroscopic or microscopic. Cystic components were estimated as <50% and ≥50% tumor volume. WHO/Hochwald grade and presence of metastases were used to stratify disease aggression. Associations were tested with Chi square/Fishers exact test and differences were tested with t-test/Wilcoxon rank sums test. RESULTS There is moderate agreement between CT and histology for presence of cystic components. Discrepancies were mostly attributable to the presence of microscopic cystic components in tumors appearing solid on CT. There was no difference in size between cystic and solid tumors on CT or pathology. No association between CT-determined cystic components and tumor grade was found. Tumors with cystic components (cystic by CT, and macroscopically cystic by pathology) demonstrated less association with metastases than solid tumors. CONCLUSIONS Cystic components, comprising ≥50% of the tumor by CT and observed macroscopically on pathology, are associated with less aggressive disease.

Formulating a Treatment Plan in Suspected Lymphoma: Ultrasound-Guided Core Needle Biopsy Versus Core Needle Biopsy and Fine-Needle Aspiration of Peripheral Lymph Nodes: Diagnostic Yield of CNB Versus FNA in Suspected Lymphoma

Image‐guided tissue sampling in the workup of suspected lymphoma can be performed by core needle biopsy (CNB) or CNB with fine‐needle aspiration (FNA). We compared the yield of clinically actionable diagnoses between these methods of tissue sampling.

Distinct clinical and magnetic resonance features of metastatic hepatocellular carcinoma treated with pembrolizumab: A case report of late response after pseudoprogression

There are few effective therapies for unresectable or metastatic hepatocellular carcinoma. Recent data have demonstrated efficacy of immune checkpoint blockade in this difficult to treat disease; however, clinical experience is limited. We report a case of hepatocellular carcinoma displaying pseudoprogression followed by a late response with novel magnetic resonance imaging features following treatment with the anti‐programmed cell death protein 1 agent pembrolizumab. (Hepatology Communications 2018;2:148–151)