![]() A Study of Courage and Hope. Median survival for patients with metastatic pancreatic adenocarcinoma is on the order of a mere 3 to 6 months. The following report of long- term survival of a patient with this devastating malignancy illustrates a highly unusual case study of hope, courage, and determination. It is the author’s hope that this report might in some way prove inspirational to patients battling this demoralizing disease and provide encouragement to those physicians who treat them. The concept of weekly “metronomic” dosing of chemotherapy is also discussed, as well as targeted therapy for the treatment of pancreatic carcinoma and other cancers. CASE REPORTPatient A. B. is a young gentleman who presented in August 2. Initial workup included a computed tomography (CT) scan of the abdomen on August 2. The patient underwent an exploratory laparotomy with biopsy of the liver lesion, cholecystectomy, and a Roux- en- Y gastrojejunostomy as a palliative bypass. Median survival for patients with metastatic pancreatic adenocarcinoma is on the order of a mere 3 to 6 months. The following report of long-term survival of a. Magnetic resonance imaging (MRI) scans are commonly used in hospitals. Here we explain how they work and what happens during and after an MRI scan. What is Positron Emission Tomography – Computed Tomography (PET/CT) Scanning? Positron emission tomography, also called PET imaging or a PET scan, is a type of. ![]() ![]() Pathology revealed an adenocarcinoma, metastatic, of unknown primary, most likely from a pancreatic primary (Figure 1). Original biopsy specimens of the metastatic liver lesion. Analysis revealed metastatic adenocarcinoma, most likely from a pancreatic primary. The patient was treated with gemcitabine and capecitabine from October through November, suffering significant side effects and evidence of disease progression. He was then switched to gemcitabine and docetaxel on December 1. A CT scan performed on January 1. Figure 2). By this time, the patient was severely ill and debilitated, and hospice was suggested. Baseline computed tomography (CT) images from January 2. The patient and his wife visited our clinic on January 2. He was confined to a wheelchair at the time and had an Eastern Cooperative Oncology Group (ECOG) score of 4. He was informed that his prognosis was indeed quite poor, especially since no standard treatment existed for metastatic pancreatic carcinoma after failing a gemcitabine- based regimen. Nevertheless, his desire was to continue treatment. Because of his young age and our experience with “metronomic” chemotherapy dosing, he was offered a salvage regimen consisting of weekly metronomic dosing of paclitaxel 6. FU) 4. 25 mg/m. 2 (POLF), which he started on January 3. To prevent neuropathy, calcium and magnesium, as well as glutathione, were given intravenously; glutamine was administered orally. The patient, who was receiving care at a nursing home, required paramedic transportation on a stretcher to and from the clinic for his treatment sessions. Many of his caregivers felt at the time that treatment was futile and encouraged him to accept hospice care. Despite the odds, however, he insisted on continuing treatment. The patient tolerated the treatment extremely well, with virtually no side effects, receiving 4 weeks of the POLF regimen before his chemotherapy had to be held because of low blood cell counts, at which time he received a dose of cetuximab in the hope that the epidermal growth factor receptor (EGFR) inhibitor might contribute to control of his disease. After receiving cetuximab, the patient developed a moderate rash, a common side effect of HER1/EGFR- targeted agents. Chemotherapy with POLF continued, along with intermittent cetuximab. Remarkably, a CT scan of the patient’s liver performed on April 2. His CA 1. 9. 9 had also decreased from a pretreatment level of 4. U/m. L to a normal 1. U/m. L. The patient continued to receive chemotherapy as the size of tumors in both his liver and pancreas continued to decrease (Figure 3). As his performance status improved, he was able to begin physical therapy. With encouragement and support from his family, Mr. A. B. continued to improve clinically. CT scans performed in April 2. Throughout the first 4 months of treatment (during which time he was hospitalized twice), the patient continued to require transportation on a stretcher. Subsequently, he was able to be transported in a wheelchair. As he continued to improve, he was eventually able to ambulate with a walker, then a cane; ultimately, the patient was able to walk without any assistance. He continued treatment for 5. POLF chemotherapy and intermittent cetuximab. Of note, the patient developed only mild neuropathy, which resolved off treatment. On March 2. 8, 2. Gastrointestinal Tumor Board at Swedish Hospital in Seattle, where his pathology reports and scans were reviewed. Because of his unusually long survival, doubts arose as to the original diagnosis of metastatic pancreatic adenocarcinoma. The diagnosis, however, was confirmed. Follow- up positron emission tomography (PET)/CT scans showed only a 2- cm lesion remaining in the liver, and no residual disease in the pancreas, nor any other evidence of disease. The patient was evaluated as a possible candidate for resection of the remaining lesion in the liver. After careful deliberation—which included consultations with surgeons in the United States and Europe—it was decided that (1) the risk of significant morbidity and mortality was too high, given this patient’s previous surgery (which included accidental laceration of an artery with need for immediate repair), and (2) the potential benefit of surgery for his metastatic disease was deemed questionable. Further chemotherapy was recommended, but it remained to be decided which regimen would be most appropriate. Ultimately, the patient was switched to weekly paclitaxel/irinotecan/oxaliplatin on May 9, with intermittent cetuximab until August 2. Subsequently he was treated with erlotinib and low- dose interferon, weekly paclitaxel and gemcitabine, and then again with weekly POLF from October 1. February 4, 2. 00. On February 5, a PET/CT scan showed a small lesion in the pancreas and a 1. Figure 4). Follow- up PET/CT scan on August 5, however, showed two hypermetabolic lesions in the tail of the pancreas measuring 2. February 2. 00. 8 PET/CT scan showed a small lesion in the pancreas and a 1. The patient’s case was again presented to the Gastrointestinal Tumor Board at Swedish Hospital on August 1. The recommendation of the Tumor Board was to rebiopsy one of the lesions in the pancreas to reconfirm the diagnosis of a metastatic pancreatic adenocarcinoma. The patient underwent endoscopic ultrasound with a transgastric biopsy of one of the lesions at the tail of the pancreas on August 2. Histopathologic analysis again revealed an adenocarcinoma with minimal staining for synaptophysin, excluding a predominantly neuroendocrine differentiated neoplasm and reconfirming the original diagnosis of pancreatic adenocarcinoma (Figure 5). In addition, KRAS testing was performed, which demonstrated the presence of the wild- type (or nonmutated) gene in the specimen. The patient resumed further treatment with weekly paclitaxel/cisplatin/irinotecan plus cetuximab, with good disease control. Histopathologic analysis of the pancreatic lesion specimens obtained in August 2. Five years out from his diagnosis of metastatic pancreatic adenocarcinoma, Mr. A. B. is doing extremely well—his current ECOG score is 0, he has returned to work, and he recently completed the “Seattle to Portland” bicycle marathon, a distance of 1. DISCUSSIONThe rationale behind treatment with a weekly “metronomic” dosing of POLF is that, though there is no standard chemotherapy beyond first- line chemotherapy with a gemcitabine- based regimen, both oxaliplatin and leucovorin/5- FU have shown activity in this disease. A recently reported phase III trial also supports the use of these agents. Dr. Margaret Tempero from the University of California, San Francisco, as spokesperson for the National Comprehensive Cancer Network, has also recommended oxaliplatin and a fluorinated pyrimidine as second- line treatment for metastatic pancreatic carcinoma after failure of a gemcitabinebased chemotherapy. Paclitaxel, especially when administered on a weekly metronomic schedule, may also have activity in pancreatic cancer,1. Endo. TAG- 1) in combination with gemcitabine. A more steady, metronomic dosing can result in fewer side effects, leading to better tolerability, but also increased efficacy due to the increased dose density and dose intensity that can be achieved compared to “traditional” chemotherapy. The importance of dose density and dose intensity in achieving chemotherapy efficacy is well known. In addition, the metronomic dosing of chemotherapy may have antiangiogenic properties due to its effects on endothelial cells,1. Causes and imaging features of false positives and false negatives on 1. F- PET/CT in oncologic imaging[1. F] 2- fluoro- 2deoxy- D- glucose (1. F- FDG) PET- CT imaging has become firmly established as an excellent clinical tool in the diagnosis, staging and restaging of cancer. F- FDG (a glucose analog) is taken up by cells via glucose transporter proteins. The glucose analog then undergoes phosphorylation by hexokinase to FDG- 6 phosphate. Unlike glucose, FDG- phosphate does not undergo further metabolism and so becomes trapped in the cell as the cell membrane is impermeable to FDG- 6 phosphate following phosphorylation [1]. Malignant tumors have a higher metabolic rate and generally express higher numbers of specific membrane transporter proteins than normal cells. This results in increased uptake of 1. F- FDG by tumor cells and forms the basis of FDG- PET imaging [2]. Glucose however acts as a basic energy substrate for many tissues, and so 1. F- FDG activity can be seen both physiologically and in benign conditions. In addition, not all tumors take up FDG [3–5]. The challenge for the interpreting physician is to recognize these entities and avoid the many pitfalls associated with 1. F- FDG PET- CT imaging. In this article we discuss false- positive and false- negative 1. F- FDG PET- CT findings, common and atypical physiological sites of FDG uptake, and benign pathological causes of FDG uptake. We will focus on post- treatment conditions that can result in false- positive findings. We will highlight the importance of utilizing the CT component of the study, not only for attenuation correction but also in the interpretation of the study. The CT component of 1. F- FDG PET- CT imaging can provide high- resolution anatomical information, which enables more accurate staging and assessment. For the purposes of this article, we refer to the descriptive terms “false- positive” and “false- negative” findings in the context of oncology imaging. The authors acknowledge that there are recognized causes of FDG uptake that are not related to malignancy; however in this paper we refer to false- positive findings as FDG uptake that is not tumor related. Patient preparation. Tumor uptake of FDG is reduced in the presence of raised serum glucose as glucose competes with FDG for uptake by the membrane transporter proteins. In order to prevent false- negative results, it is necessary for the patient to fast for at least 4–6 h prior to the procedure [6]. Induction of a euglycamic hypoinsulinaemic state also serves to reduce the uptake of glucose by the myocardium and skeletal muscle. In the fasting state, the decreased availability of glucose results in predominant metabolism of fatty acids by the myocardium. This reduces the intensity of myocardial uptake and prevents masking of metastatic disease within the mediastinum [6]. The radiotracer is administered intravenously (dose dependent on both the count rate capability of the system used and the patient’s weight), and the patient is left resting in a comfortable position during the uptake phase (6. Patient discomfort and anxiety can result in increased uptake in skeletal muscles of the neck and paravertebral regions. Muscular contraction immediately prior to or following injection can result in increased FDG activity in major muscle groups [6]. Patients are placed in a warm, quiet room with little stimulation, as speech during the uptake phase is associated with increased FDG uptake in the laryngeal muscles [7]. At our institution we perform the CT component with arms up except for head and neck studies where the arms are placed down by the side. This minimizes artifacts on CT. Depending on the type of cancer, oral contrast to label the bowel and intravenous contrast may also be given. The CT is performed with a full dose similar to a diagnostic CT, and lungs are analyzed following reconstruction with a lung algorithm. The PET scan is performed with 3–4 min per bed position; however the time per bed position will vary in different centers depending on both the dose of FDG administered and the specifications of the camera used for image acquisition. It is beyond the scope of this article to provide detailed procedure guidelines for 1. F- FDG PET- CT imaging, and for this purpose we refer the reader to a comprehensive paper by Boellaard et al. Technical causes of false positives. Misregistration artifact The evaluation of pulmonary nodules provides a unique challenge for combined PET- CT scanning due to differences in breathing patterns between CT and PET acquisition periods. CT imaging of the thorax is classically performed during a breath- hold; however PET images are acquired during tidal breathing, and this can contribute significantly to misregistration of pulmonary nodules on fused PET- CT images. Misregistration is particularly evident at the lung bases, which can lead to difficulty differentiating pulmonary nodules from focal liver lesions (Fig. 1) [9]. F- FDG PET- CT performed in a 6. On the coronal PET images, a focus of increased FDG uptake is seen at the right lung base (black arrow). Contrast CT does not show any pulmonary nodules but does demonstrate a liver.. Acquiring CT imaging of the thorax during quiet respiration can help to minimize misregistration artifacts. It is also important to correlate your PET and CT findings by scrolling up and down to make sure that lesions match. Injected clot A further diagnostic pitfall in staging of intrathoracic disease can be caused by injected clot. Injection of radioactive clot following blood withdrawal into the syringe at the time of radiotracer administration can result in pulmonary hotspots [1. The absence of a CT correlate for a pulmonary hotspot should raise the possibility of injected clot; however this is a diagnosis of exclusion, and it is important to carefully evaluate the adjacent slices to ensure the increased radiotracer activity does not relate to misregistration of a pulmonary nodule or hilar lymph node. The area of abnormal radiotracer uptake should also be closely evaluated on subsequent restaging CT to ensure there has been no interval development of an anatomical abnormality in the region of previously diagnosed injected clot (Fig. 2) [1. F- FDG PET- CT performed in a 2. A focus of increased FDG uptake (yellow arrow) is identified in the left lower lobe with no CT correlate (a). A 3- month follow- up CT thorax again does not demonstrate any.. Injection artifact Leakage of radiotracer into the subcutaneous tissues at the injection site or tissued injection can result in subcutaneous tracking of FDG along lymphatic channels in the arm. This can result in spurious uptake in axillary nodes distal to the injection site [1. Careful attention must be paid to the technical aspects of the study to ensure accurate staging. Injection at the side contralateral to the site of disease is advised where feasible to allow differentiation between artifactual and metastatic uptake, particularly in breast cancer patients. The side of injection should also be clearly documented during administration of radiotracer, and this information should be available to the reader in order to ensure pathological FDG uptake is not spuriously attributed to injection artifact (Fig. 3). F- FDG PET- CT performed in a 5. Some low grade FDG uptake is identified in non- enlarged right axillary nodes (yellow arrow) consistent with injection artifact. Imaging of metallic implants The use of CT for attenuation correction negates the need for traditional transmission attenuation correction, reducing scanning time. There are however technical factors relating to the use of CT imaging for attenuation correction, which lead to artefacts when imaging metal [9]. The presence of metal implants in the body produces streak artifact on CT imaging and degrades image quality. When CT images are used for attenuation correction, the presence of metal results in over attenuation of PET activity in this region and can result in artifactual ‘hot spots.’ Metal prostheses, dental fillings, indwelling ports and breast expanders and sometimes contrast media are common causes of streak artifact secondary to high photon absorption and can cause attenuation correction artifacts [9]. In order to avoid false positives, particularly when imaging metallic implants careful attenuation should be paid to the nonattenuation corrected images, which do not produce this artifact. Sites of physiological FDG uptake.
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November 2017
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