PET/CT N E W S L E T T E R Issue No.11 October 2010 P ET/CT Newsletter is a free publication dedicated to informing and educating medical professionals on the topic of molecular imaging. Thank you for your interest and we hope you find our newsletter stimulating and informative. Table of Contents In the News ...............................p 1 - 3, 5-7 Case Study of the Month ...........................................p 4 Bimonthly Next Issue: December 2010 In The News PET/CT detects early eﬃcacy of chemo drug in NSCLC patients By Wayne Forrest AuntMinnie.com staﬀ writer September 17, 2010 Dutch researchers have found that FDG-PET/CT can identify early response to preoperative chemotherapy with erlotinib in most patients with non-small cell lung cancer (NSCLC), potentially avoiding unnecessary toxicity from ineﬀective treatment, according to a study in the September issue of the Journal of Nuclear Medicine. Though the study was relatively small, the researchers from four hospitals in the Netherlands concluded that the results are promising and consistent with the results of preclinical studies. The lead author was Tjeerd Aukema, MD, from the department of nuclear medicine at Haga Hospital in the Hague (JNM, September 2010, Vol. 51:9, pp. 1344-1348). Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been used over the past several years to treat non-small cell lung cancer. Previous research has found that the moleculartargeted agent can prompt early responses to treatment in certain patients with NSCLC and prolong survival when administered as a second-line treatment in advanced cases. NSCLC survival The survival rate for NSCLC patients has not improved greatly over the past few years, the authors wrote, and the number of patients presenting with stage IV disease has increased. They noted that the advance is likely the result of better staging, as the metastatic disease is identified prior to clinical symptoms, in part, through FDG-PET’s ability to determine oncologic staging. Positron Emission Tomography (PET) is a non-invasive diagnostic imaging procedure that can provide unique information for accurate TNM staging. Many cancers exhibit increased glucose metabolic rates which can be identified with PET via the radio-pharmaceutical 18F-FDG. Since changes in glucose metabolism often occur before changes in anatomy (e.g. tumor growth), PET can often identify the presence of disease earlier than other anatomic imaging techniques. Early disease identification is particularly critical during the assessment of nodal involvement or the determination of the presence of metastatic disease. additional endoscopic ultrasound-guided fine-needle aspiration cytology or mediastinoscopy was used. Erlotinib treatment The patients received preoperative erlotinib (150 mg) once daily for three weeks, with FDG-PET/CT scans performed before and after erlotinib administration to obtain both baseline FDG-PET/CT and follow-up results. The median time between the start of erlotinib therapy and follow-up FDG-PET/CT imaging was six days. The baseline FDG-PET/CT scans (Gemini TF, Philips Healthcare, Andover, MA) were obtained during routine staging in all patients with FDG doses of 180 to 240 MBq. Low-dose CT images also were acquired without intravenous contrast. The median time between these two scans was 21 days. The researchers measured changes in tumor FDG uptake during treatment by prospectively assessing standardized uptake values (SUVs). Patients with a decrease in SUV of 25% or more after one week were classified as “metabolic responders.” Their metabolic response was compared with the pathologic response, which was obtained through histopathologic examination of resected specimens. SUV comparisons Aukema and colleagues found the median SUVmax at baseline FDG-PET/CT to be 11.0, while the median SUVmax after one week of erlotinib therapy was 9.3. In addition, six (26%) of the 23 cases had a partial response within one week, 16 patients (70%) had stable disease, and one patient (4%) had progressive disease. Therefore, they hypothesized that FDG-PET/CT may be a “valuable clinical predictor” for early response to preoperative erlotinib treatment. The study enrolled eight men and 15 women (mean age, 63 years) from October 2006 to March 2009. All 23 patients were diagnosed with stage I to stage III nonsmall cell lung cancer and were eligible for surgical resection. They also were part of an ongoing phase II trial at the four Dutch hospitals of the researchers. Staging procedures included contrast-enhanced CT and PET/CT scans. With mediastinal metabolic uptake or nodes greater than 1 cm in the shortest diameter, Coronal FDG-PET images show a patient with carcinoma in the left lung. Maximum intensity projection (MIP) images before (A) treatment with erlotinib show a reduction in uptake (ΔSUVmax, -57%) and increase in necrosis of primary tumor after seven days (B) of treatment with erlotinib. The results are also noted in transverse PET/CT fusion images before (C) and after seven days (D) of erlotinib. After erlotinib treatment, the patient was operated on; the resected specimen contained 80% necrosis. Image courtesy of the Journal of Nuclear Medicine. In the News (continued) FDG-PET/CT also revealed a median 40% necrosis in the resection specimens of treated patients. Among patients classified as metabolic responders, the median percentage necrosis was 70%, compared with a median 40% necrosis among metabolic nonresponders. The prospective study suggests that during the course of preoperative erlotinib treatment for NSCLC patients, FDG- PET/CT “can identify response in most patients,” the authors concluded. “Even though our study was relatively small, the results are promising and consistent with the results of preclinical studies.” They recommended that additional data from larger groups of patients are needed to definitively determine “the optimal timing of response evaluation and the relevance of cutoﬀ values of response parameters.” PET-CT Can Detect Asymptomatic Recurrence of Head and Neck Cancer: Presented at AAO-HNSF By Cheryl Lathrop September 30, 2010 BOSTON -- September 30, 2010 -- Positron emission tomography (PET) and conventional computed tomography (CT) is an eﬀective tool for detecting early asymptomatic recurrent disease, according to a study presented here on September 27 at the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) Annual Meeting 2010. Head and neck cancer patients are at greatest risk of recurrence within the first 5 years of treatment, but early detection of recurrent disease in patients with a benign exam, and no symptoms, is a challenge, according to findings presented during a poster session by Mark Varvares, MD, Department of Otolaryngology-Head and Neck Surgery, St. Louis University, St. Louis, Missouri, and colleagues. Previous studies have shown the PET-CT imaging modality to be more accurate than PET alone. And, it could detect disease that would otherwise not be identified upon physical exam or by patient-reported symptoms. The researchers recently reported the eﬀectiveness of fluorodeoxyglucose (FDG) PET-CT in detecting an asymptomatic recurrence in a group of previously treated head and neck cancer patients. This report is a follow-up study reporting the survival outcomes in this group once the recurrence was detected. A retrospective review was performed on a series of head and neck cancer patients (n = 123) at a single institution between February 2004 and July 2007 who had undergone non-staging FDG-PET-CT scans as an integral part of the patient’s follow up after having received definitive treatment. Each scan (n = 308) was evaluated by a board-certified nuclear medicine physician and final scan readings from each patient’s medical record were reviewed for this study. Lesions were defined as primary, regional, or distant site. Each positive lesion was confirmed clinically or histologically, and each positive lesion was then retrospectively defined as symptomatic or asymptomatic Page 2 based on clinic notes. Lesions were considered to be an asymptomatic recurrence if the patient had no symptoms or physical findings at the time of the scan. The patients who were identified as having an asymptomatic recurrence were then followed until the time of their last follow-up visit, or death. The majority of patients evaluated had squamous cell carcinoma of the oral cavity, pharynx, and larynx. There were 96 (78%) male patients and 27 (22%) female patients. A total of 616 lesions on 308 scans were evaluated. Of those scans, 25 (8%) detected asymptomatic disease; 33 (5%) represented asymptomatic recurrent disease. Asymptomatic lesions were detected most frequently at distant sites with 52% being thoracic, but also included primary (6%), regional (9%), and other (33%) sites. These lesions were found in 24 (20%) of the patients evaluated. At last follow-up of the 24 patients where asymptomatic recurrence was detected, 9 remain alive, 5 with disease. The remainder of the group has died of malignant disease. “Determining an eﬀective surveillance regimen is the goal for future management of head and neck malignancies; prospective studies are necessary to determine if PETCT imaging modality will be part of this routine,” Dr. Varvares noted. FDG-PET/CT viability scans detect vulnerable aortic plaque By Wayne Forrest AuntMinnie.com staﬀ writer September 27, 2010 Canadian researchers have found that detecting vulnerable aortic plaque with conventional FDG-PET/ CT myocardial viability studies is feasible, according to a presentation at the American Society of Nuclear Cardiology (ASNC) annual meeting in Philadelphia. The group, from the University of Ottawa Heart Institute in Ottawa, Ontario, also found that the rate of very positive FDG uptake among patients with ischemic heart disease is low, which reflects aggressive secondary risk factor modification through statins and lip-lowering drugs. FDG-PET/CT myocardial viability scans are routinely used on patients with severe coronary artery disease and left ventricular dysfunction, because FDG accumulates in areas with high levels of metabolism including vulnerable aortic plaque, according to the researchers. The three images represent clinical myocardial FDGPET/CT viability studies, which show Grade 0 or negative aortic FDG uptake (A), Grade 1 or mildly positive aortic FDG uptake (B), and Grade 2 or very positive aortic 18-FDG uptake (C). Images courtesy of the University of Ottawa Heart Institute. Statins also have been shown to significantly reduce the degree of aortic FDG uptake. “Since the imaging window of FDG-PET/CT scans includes the aorta, we evaluated the feasibility of vulnerable plaque detection using the cardiac FDG-PET viability studies,” noted senior study author Terrence Ruddy, MD, director of nuclear medicine at the Heart Institute and head of nuclear medicine at Ottawa Hospital, and colleagues. Myocardial viability scans The researchers retrospectively analyzed FDG uptake in 30 consecutive patients, 24 men and six women, who received FDGPET myocardial viability scans and had a history of coronary artery disease. In addition, 28 of the 30 patients were being treated with statins or other lipid-lowering agents. PET/CT, Prostate Cancer After Surgery MDNews.com By: Jeﬀ Muise Friday, August 27, 2010 All 30 myocardial viability studies were reconstructed with PET and CT registration based on extracardiac landmarks to avoid attenuation correction artifacts. The study also used the lumen of the descending thoracic aorta to determine the blood pool standard uptake value (SUV) of FDG. (HealthDay News) — Positron emission tomography/computerized tomography (PET/CT) to detect [11C]choline uptake appears to be useful for re-evaluating prostate cancer disease stage for men who have increasing prostate-specific antigen (PSA) levels after radical prostatectomy and no evidence of disease on conventional imaging, according to a study in the September issue of The Journal of Urology. The researchers then evaluated the areas of FDG uptake and activity relative to blood pool. Grade 0 or negative evaluation was given to areas with no activity, or if the average SUV to blood pool average SUV ratio was less than 1.25. Grade 1 or mildly positive activity indicated a ratio of average SUV to blood pool average SUV of 1.25 to 1.50. Grade 2 or very positive activity indicated that the ratio of average SUV to blood pool average SUV was greater than 1.50. Giampiero Giovacchini, M.D., of the University of Milano-Bicocca in Italy, and colleagues studied 109 patients who had PSA levels above 0.2 ng/mL after radical prostatectomy, no lymph node disease at prostatectomy, no evidence of metastatic disease on conventional imaging, no androgen deprivation therapy, and no radiotherapy. The subjects underwent [11C]choline PET/CT to re-evaluate their prostate cancer disease stage. FDG uptake The analysis found that six (17%) of the 30 studies had grade 2 or very positive FDG uptake, while 19 studies (63%) had grade 1 or mildly positive FDG uptake. The remaining five studies (17%) had little or no FDG uptake. The researchers found that the PSA counts in the group at time of imaging ranged from 0.22 to 16.76 ng/mL (median 0.81 ng/mL). Based on the PET/CT imaging, local recurrence was diagnosed in four patients (4 percent) and pelvic lymph node disease in eight patients (7 percent). Scans were positive in 5 percent of patients with PSA less than 1 ng/mL, 15 percent with PSA between 1 and 2 ng/mL, and 28 percent with PSA greater than 2 ng/mL. Five of the six patients with grade 2 or very positive uptake were on a lipid-lowering agent. In addition, 19 of 20 patients with grade 1 mildly positive uptake were on a lipid-lowering agent. All five patients with grade 0 negative uptake were on a lipid-lowering agent. Based on the results, Ruddy and colleagues concluded that detecting vulnerable aortic plaque with conventional FDG-PET/CT viability scans is feasible. “The rate of very positive uptake in this population of ischemic heart disease patients is low, reflecting aggressive secondary risk factor modification” and showing the value of statins and lipid-lowering agents. “Positron emission tomography/computerized tomography detected increased [11C]choline uptake, suggesting recurrent disease in 11 percent of patients with prostate cancer, increasing PSA after radical prostatectomy, and no evidence of disease on conventional imaging. This modality may be useful to restage disease but it cannot be used to guide therapy,” the authors write. Page 3 Case Study of the month 18 F-NaF PET bone imaging vs. planar 99mTc MDP in a patient with breast cancer The following case (Figure 1 and Figure 2 ) shows a patient with a history of breast cancer who presented with increasing back pain two weeks after a fall. The 99mTc-MDP planar bone scan showed increased uptake in the body of the L2 vertebrae, which suggested the possibility of post-traumatic fracture or metastatic disease. A minimal focal uptake in the left 7th rib was also similarly equivocal. MRI of the lumbar spine showed focal marrow hyperintensities, which were suspicious for bone metastases. An 18F-FDG PET scan was performed, which showed no abnormal vertebral lesion. In view of the fact that FDG PET is often normal in presence of purely sclerotic bone metastases, a 18F-NaF PET scan was ordered. The 18F-NaF scan revealed abnormal uptake consistent with metastatic disease in the vertebral body of the L2 vertebra. Additional foci were noted in vertebral bodies L3, L5, the superior end plate of L4, and the right transverse process of L3; all were consistent with metastatic bone disease that was not visualized in the FDG PET scan. Numerous lesions that were identified in the pelvis were appreciated only in retrospect on a prior CT scan. Focal uptake in the left 7th rib and right glenoid were consistent with metastatic disease. An additional focus of activity was seen in the proximal metaphysis of the right femur that was faintly visualized on the bone scan. Figure 1. 18F-NaF PET bone imaging vs. planar 99mTc MDP in a patient with breast cancer Data courtesy David Haseley, MD and Gustavo Mercier, MD, Seattle Nuclear Medicine, Seattle, WA 99m Tc MDP Bone Scan 18 F-FDG PET Page 4 Continued on page 5 Figure 2. 18F-NaF PET bone imaging vs. planar 99mTc MDP in a patient with breast cancer - continued Data courtesy David Haseley, MD and Gustavo Mercier, MD, Seattle Nuclear Medicine, Seattle, WA 99 mTc MDP Bone Scan 99 mTc MDP 18 18 F-FDG F-NaF Page 5 Study combines FDG-PET/ CT with circulating tumor cell counts The retrospective study reviewed the M. D. Anderson breast medical oncology database and identified patients who had received systemic treatment for bone metastases from breast cancer between December 2004 and May 2008, as well as patients with intrathoracic lymph node or chest wall metastases in addition to bone metastases. Patients with visceral metastases were excluded. All 55 patients enrolled in the study underwent FDGPET/CT scans (Discovery ST, STE, or RX, with 8-, 16-, or 64-slice CT, GE Healthcare, Chalfont St. Giles, U.K.) and CTC evaluation within three weeks before starting a new treatment. By Wayne Forrest AuntMinnie.com staﬀ writer August 26, 2010 August 26, 2010 -- Although FDG-PET/CT is useful for monitoring patients with bone metastases from breast cancer, additional prospective studies are needed to define the roles of FDG-PET/CT and circulating tumor cells in measuring the disease, according to a new study in the August issue of the Journal of Nuclear Medicine. Circulating tumor cells (CTCs) are cells that can break from a tumor, travel through the bloodstream, and eventually become tumors in organs such as the breast, liver, or colon. The presence of CTCs before treatment is a predictor of progression-free survival and overall survival in patients with metastatic breast cancer. Researchers from M. D. Anderson Cancer Center at the University of Texas in Houston found that CTC counts at follow-up agreed with FDG-PET/CT assessment in 78% of the study’s patients. In addition, FDG-PET/CT findings and follow-up CTC counts were “significantly associated with both progression-free survival and overall survival.” The lead author of the study was Ugo De Giorgi, MD, from the department of breast medical oncology at M. D. Anderson (JNM, August 2010, Vol. 51:8, pp. 1213-1218). CTC numbers Another study by De Giorgi and colleagues, published earlier this year in the Annals of Oncology, found that the presence of extensive bone metastases as detected by FDG-PET/CT was associated with increased CTC numbers in metastatic breast cancer (Ann Oncol, January 2010, Vol. 21:1, pp. 33-39). “Specifically, we showed that CTC numbers were higher in patients with bone metastases than in those with no bone lesions and higher in patients with three or more old metastases than in those with fewer bone lesions,” the authors wrote. With that as the foundation, the authors launched a new study to compare the predictive significance of FDG-PET/ CT and CTC counts in patients with bone metastases from breast cancer treated with standard systemic therapy. Page 6 Twenty-six patients received systemic therapies for bone metastases only, and 29 patients received treatment for bone metastases and intrathoracic lymph node or chest wall metastases after undergoing both CTC and PET/CT evaluation. Thirty-six patients (65%) had received prior treatment for metastatic breast cancer with hormone therapy (23 cases), chemotherapy with or without hormone therapy (nine cases), or HER2-targeted therapies with chemotherapy or hormone therapy (four cases). Nineteen patients (35%) had newly diagnosed metastatic breast cancer. Disease progression In their analysis, the researchers found CTC count at follow-up agreed with the FDG-PET/CT assessment for nonprogressive disease or progressive disease in 43 patients (78%). Among the remaining patients, four patients (33%) with fewer than five circulating tumor cells per 7.5 mL of blood at follow-up were found to have evidence of progressive disease by FDG-PET/CT, compared with eight patients (67%) with persistent CTCs (≥ 5 CTCs/7.5 mL of blood) at follow-up who did not have evidence of progressive disease. In all 55 patients, the mean for progression-free survival was 10.5 ± 7.2 months, ranging from two to 34 months. The mean overall survival was 18.1 ± 6.7 months, with a range of three to 37 months. At the time of analysis, seven patients (13%) were considered progression-free, with an average followup time of 18 months, ranging from 10 to 34 months. Eighteen patients (33%) had died. Follow-up CTC counts and FDG-PET/CT assessment for nonprogressive or progressive disease were found to be significantly associated with both progression-free and overall survival. The researchers also concluded that baseline CTC count was “not a significant predictor for either progression-free survival or overall survival.” The group also found that median progression-free survival was 13 months in patients with both < 5 CTCs/7.5 mL of blood and FDG-PET/CT nonprogression. The median progression-free survival was six months in patients with < 5 CTCs/7.5 mL of blood or FDG-PET/CT nonprogression, but not both, while the median progression-free survival was five months in patients with neither < 5 CTCs nor FDG-PET/CT nonprogression. “The multivariate analysis indicated that FDG-PET/ CT was the only predictive sign,” De Giorgi and colleagues wrote. “However, the combination of FDG-PET/CT and CTC might be a useful tool to monitor response to therapy in patients without measurable extraosseous disease, especially in patients with elevated CTC at baseline.” They also noted that the discordance of FDG-PET/CT assessment and CTC count “needs to be evaluated in a prospective study to determine the value of FDG-PET/CT and CTC individually and in combination.” “A prospective study could validate the benefit of these two approaches used separately and in combination in determining prognosis, monitoring response, and establishing bone-dominant disease as a tumor response-measurable disease,” they wrote. F-18 ﬂuoride PET/CT may offer one-stop shop for bone metastases [U.S. Food and Drug Administration] for clinical use and distribution, so PET centers could make use of this useful test profitably.” Skeletal PET gains support for pediatric bone scans By Cynthia E. Keen AuntMinnie.com staﬀ writer April 15, 2010 BOSTON - Skeletal scintigraphy with F-18 sodium fluoride (F-18 NaF) is a safe and eﬀective way to diagnose skeletal disorders in children and could be used instead of bone SPECT exams, according to research presented on Wednesday at the Society for Pediatric Radiology (SPR) meeting. Skeletal PET bone imaging fell into disuse in the 1970s after SPECT imaging with technetium sodium chloride was introduced, said Dr. Frederick Grant of the division of nuclear medicine at Children’s Hospital Boston. But tight supplies of technetium, caused by the ongoing global shortage of molybdenum, have many nuclear imaging specialists re-examining the technology. Children’s Hospital Boston began to use F-18 NaF scintigraphy routinely in 2005 and has had very positive experiences, Grant said. In his SPR presentation, he reported results from a retrospective study of 484 patients between infancy and 19 years of age who had the procedure between April 2005 and March 2010, with skeletal scintigraphy showing positive findings for 57%. In the study, 87% of patients had the exam due to back pain -- often due to sports injuries -- and, of these, 186 of 350 young athletes had positive exam findings. Other indications included back pain after trauma (13 patients with 54% positive findings), persistent back pain after spinal fusion surgery (33 patients with 61% positive findings), and metastatic disease. In most cases, images were of higher resolution than with conventional SPECT, Grant said. By Wayne Forrest AuntMinnie.com staﬀ writer November 3, 2009 Monday, November 30 | 11:10 a.m.-11:20 a.m. | SSC09-05 | Room S504CD Researchers from India will discuss a study that showed that PET/ CT with F-18 fluoride beat other nuclear medicine techniques for detecting skeletal lesions, as well as for distinguishing between benign and malignant tumors, in patients at high risk for skeletal metastases. A total of 46 children younger than 2 who had indications of nonaccidental trauma had positive findings 89% of the time. Grant attributed this to selection bias, as these were patients suspected of being victims of child abuse. Because of their very young age, these children required sedation for the procedure. Researchers at Tata Memorial Hospital in Parel, Mumbai, also found that F-18 fluoride PET/CT had the least number of equivocal lesions compared to technetium-99m methylene diphosphonate (MDP) planar, SPECT, and SPECT/CT studies, due to the increased sensitivity of fluoride over MDP and also due to the morphological detail provided by CT. For all patients, PET was performed 30 minutes after administration of 21 MBq per kg (with a maximum of 148 MGq) F-18 NaF. Grant recommended that patients be well hydrated. The imaging procedure took 30 minutes or less, compared to 60 to 90 minutes for a technetium bone SPECT exam, requiring an update period of up to three hours. “The study provides enough evidence for the utilization of F-18 flouride PET/CT as a one-stop evaluation of bone metastases,” said Dr. Venkatesh Rangarajan, lead author and professor in-charge of Tata’s bioimaging unit. “The short duration of acquisition and the short duration of the study is unique, and the [low] number of equivocal or inconclusive findings makes this test significantly advantageous.” “The shorter procedure time has improved department workflow, and it enables us to obtain a higher utilization rate for the PET scanner,” Grant said. “By educating medical doctors of large health insurance companies, we also get reimbursement for this. The only payor we haven’t had any success with is the Centers for Medicare and Medicaid Services, because Medicare rules strictly apply to Medicaid patients.” Given the current global shortage of molybdenum-99, Rangarajan believes that shifting from bone scans to fluoride PET/CT studies would be “a wise decision both for the patient and the doctor. F-18 flouride is a radiopharmaceutical which has been approved by the Page 7 Oncology Molecular Imaging, LLC 300 Parkbrooke Place Suite 150 Woodstock, GA 30189 www.omillc.com Oncology Molecular Imaging LLC (OMI) is a provider of comprehensive full service solutions to medical oncology practices for Positron Emission Tomography (PET) and Computed Tomography (CT). OMI partners with medical and radiation oncologists to establish in-oﬃce fixed site imaging centers, and provides development and operational services to support the imaging facilities. OMI oﬀers oncology practices a complete solution that enhances patient services while capturing revenues that would have otherwise been lost to an alternate provider. With leading capabilities in-house, patients have quicker, more convenient access to cancer care and physicians have greater control over their course of treatment. Our services are physician-centric in approach, while being patient-driven in their outcome. To learn more go to www.omillc.com If you wish to receive this newsletter electronically go to: www.omillc.com/newsletter The editorial board, editors, and writers have complete independence in the selection of content. No article has been pre disclosed to commercial supporters. Opinions and statements expressed in PET/CT Newsletter do not reflect the opinions of the Oncology Molecular Imaging, LLC (OMI) or any of it’s aﬃliates. The information provided herein is intended for educational use by physicians and other medical professionals. Inclusion of certain medications and health care practices does not constitute endorsement by Oncology Molecular Imaging, LLC. Consult the current prescribing information or a qualified medical professional before prescribing any therapy discussed. PET/CT N E W S L E T T E R Issue No.11 October 2010 Where to order a PET/CT scan in your area: Go to www.omillc.com and click on locations to see where PET/CT is available in your area.