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Preliminary Communication |

F18-Fluorodeoxyglucose–Positron Emission Tomography/Computed Tomography Screening in Li-Fraumeni Syndrome FREE

Serena Masciari, MD; Annick D. Van den Abbeele, MD; Lisa R. Diller, MD; Iryna Rastarhuyeva, MD; Jeffrey Yap, PhD; Katherine Schneider, MPH; Lisa Digianni, PhD; Frederick P. Li, MD; Joseph F. Fraumeni, MD; Sapna Syngal, MD, MPH; Judy E. Garber, MD, MPH
[+] Author Affiliations

Author Affiliations: Division of Population Sciences (Drs Masciari, Digianni, Li, Syngal, and Garber and Ms Schneider), Department of Radiology (Drs Van den Abbeele, Rastarhuyeva, and Yap), and Perini Family Survivors' Center (Dr Diller), Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (Dr Fraumeni); and Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts (Dr Syngal).


JAMA. 2008;299(11):1315-1319. doi:10.1001/jama.299.11.1315.
Text Size: A A A
Published online

Context Individuals with Li-Fraumeni syndrome (LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds.

Objective To gather preliminary data with which to evaluate F18-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds.

Design, Setting, and Participants Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill-health were offered FDG-PET/CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist.

Main Outcome Measure The primary outcome was the detection of new primary cancers using FDG-PET/CT scanning.

Results Of 15 individuals, baseline FDG-PET/CT scan identified asymptomatic cancers in 3 (20%). Two individuals had papillary thyroid cancers (stage II and stage III) and one individual had stage II esophageal adenocarcinoma.

Conclusions These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration.

Figures in this Article

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome characterized by an increased predisposition to diverse early onset malignancies, including but not limited to sarcomas, breast cancers, brain tumors, adrenal cortical carcinomas, and leukemias.1 Germline mutations in the tumor suppressor gene TP53 (tumor protein p53, chromosome 17p13; OMIM 191170) are detectable in 70% of classic LFS families.2,3 Over time, the list of neoplasms occurring excessively in LFS has expanded to include a much broader range of cancers, including gastrointestinal tract and endocrine tumors and lymphomas.47 Individuals with LFS who survive one cancer have a markedly elevated risk of additional primary neoplasms.8,9

In classic LFS, the proband must be diagnosed with a sarcoma before age 45 years, a first-degree relative with cancer before age 45 years, and another first-degree relative with soft tissue or osteosarcoma at any age, or any cancer before age 45 years.1 Li-Fraumeni–like kindreds have cancer histories meeting less stringent criteria, and a 30% chance of carrying a germline TP53 mutation.1012 In individuals carrying TP3 mutations, the risk of developing cancer has been estimated at 50% by age 30 years and 90% by age 60 years.13 In LFS, tumors can occur in any anatomic site at any age, making it difficult to identify practical, effective screening and prevention strategies.14

We explored the use of fluorodeoxyglucose F18–positron emission tomography/computed tomography (FDG-PET/CT) scanning for early detection in LFS kindreds because of its demonstrated ability to detect primary tumors as well as metastatic lesions in a wide range of neoplasms, including breast cancer, sarcomas, and aggressive brain tumors.1519

Individuals were recruited from those responding to a survey mailed to members of 60 kindreds in the LFS family registry at the Dana-Farber Cancer Institute, which includes families originally enrolled at the National Cancer Institute. Participation also was offered to individuals contacting the Dana-Farber Cancer Institute for information about LFS. Eligible individuals were members of LFS kindreds who either carried a known TP53 mutation or were obligate mutation carriers. Participants were either cancer survivors or without a prior cancer history. Exclusion criteria included a prior history of metastatic cancer or a new invasive cancer diagnosis within the previous 5 years. All participants signed informed consent, provided a medical history, underwent a physical examination, and provided complete blood counts plus differential. The study was approved by the Dana-Farber/Harvard Cancer Center institutional review board. The study was conducted from 2006 to 2007.

FDG-PET/CT Imaging and Evaluation

The FDG-PET/CT scans were performed in accordance with the clinical protocols of the Dana-Farber Cancer Institute. The European Organization for Research and Treatment of Cancer and the National Cancer Institute's guidelines on a hybrid system consisting of a combined PET/CT scanner (Biograph 16 Hi-Rez, Siemens, Knoxville, Tennessee; GE Discovery ST 16, Milwaukee, Wisconsin) were used.20,21 Individuals were instructed to avoid strenuous exercise and fast for at least 6 hours prior to being injected with approximately 20 mCi of FDG. A whole-body PET/CT scan was performed at 60 minutes postinjection of FDG. The spiral CT scan was performed with a moderate dose to enable anatomical localization in addition to correction of photon attenuation. The whole-body PET scan was performed immediately after the spiral CT scan for approximately 40 to 45 minutes (13-15 PET bed positions at 3 minutes per bed position). At the conclusion of the whole-body PET scan, a dedicated brain PET scan was performed for 15 minutes. The estimated effective dose of the entire FDG-PET/CT imaging session was approximately 2.4 rem.

A nuclear medicine physician experienced in reading FDG-PET/CT scans (A.V.D.A.) and aware of protocol eligibility criteria reviewed all images blinded to clinical history and prior clinical interpretation. Areas of increased focal FDG uptake were scored using a 5-point scale of likelihood that any finding was malignant (1, definitely benign; 2, probably benign; 3, equivocal; 4, probably malignant; 5, definitely malignant). The maximum standardized uptake values were measured for all lesions (data not shown). Data for the 3 individuals with a score of 4 or greater are reported in the Table. The protocol included a follow-up scan at 12 months (data not complete).

Table Graphic Jump LocationTable. Features of Lesions Detected by Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT)

Of the 15 asymptomatic individuals with a physical examination not suspicious for cancer and normal complete blood cell count, FDG-PET/CT scanning detected lesions in 3 (20%). The lesions were identified as being likely malignant (score ≥4) and were subsequently confirmed as malignant (Table). A focus of moderately increased tracer uptake (maximum standardized uptake value of 5.2) in the right lobe of the thyroid in a 31-year-old breast cancer survivor was a stage II papillary thyroid carcinoma with thymus involvement (T1N0M1) at thyroidectomy. An intensely FDG-avid (maximum standardized uptake value of 17) nodule in the left lobe of the thyroid of a survivor of breast cancer and sarcoma was a stage III papillary carcinoma (T3N0M0) at resection (Figure 1). Finally, a 36-year-old asymptomatic male with no prior history of cancer showed an area of focal increased uptake (maximum standardized uptake value of 5.3) at the gastroesophageal junction (Figure 2). Upper endoscopy with endoscopic ultrasound identified a stage IIA 3-cm esophageal adenocarcinoma (T3N0M0). He underwent intensive preoperative chemotherapy, radiation followed by surgery, and adjuvant chemotherapy.

Place holder to copy figure label and caption
Figure 1. Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Images of an Individual With a Thyroid Cancer
Graphic Jump Location

Whole-body maximal intensity projection image (left) and axial transverse slices through the thyroid displayed as PET (top right), CT (middle right), and fused PET/CT images (bottom right) of a patient with Li-Fraumeni syndrome showing intense FDG uptake in the left lobe. The spiral CT scan was performed with a moderate dose to enable anatomical localization in addition to correction of photon attenuation. Arrowheads indicate the location of the nodule in the left lobe of the thyroid.

Place holder to copy figure label and caption
Figure 2. Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Images of an Individual With a Gastroesophageal Junction Cancer
Graphic Jump Location

Whole-body maximal intensity projection image (left) and axial transverse slices through the gastroesophageal junction displayed as PET (top right), CT (middle right), and fused PET/CT images (bottom right) of a patient with Li-Fraumeni syndrome showing focal FDG uptake in the gastroesophageal region. The spiral CT scan was performed with a moderate dose to enable anatomical localization in addition to correction of photon attenuation. Arrowheads indicate location of adenocarcinoma at the gastroesophageal junction.

No other lesion was scored greater than 2 (probably benign) in the standardized review. Clinical FDG-PET/CT scan interpretations of lesions in 5 patients led to additional images (n = 4) or procedures (1 colonoscopy and 1 hysterectomy previously planned for fibroid tumors); all were found to be negative.

Among hereditary cancer predisposition syndromes, LFS has presented special challenges because of the early onset and diverse spectrum of cancers for which carriers have increased risk. The National Comprehensive Cancer Network guidelines (http://www.nccn.org) provide a surveillance program for adults with LFS based on expert opinion and extrapolation from other syndromes. Recommendations include annual comprehensive physical examinations with skin and neurological assessment; colonoscopy every 2 to 5 years; additional organ-targeted surveillance based on family history; and, for adult women, biannual clinical breast examinations, annual mammograms, and breast MRI screening starting at age 20 to 25 years. Definitive data are often unavailable for rare syndromes, which are hampered by selection and insufficient numbers of individuals to permit randomized designs.

In this pilot study, we tested the feasibility of using FDG-PET/CT scanning, a whole-body imaging technique, for this group of individuals who are at increased risk of developing tumors throughout the entire body. The FDG-PET/CT allows the simultaneous acquisition of information on increased glycolytic/metabolic activity in cells and organs (FDG-PET) combined with anatomical references (CT). The FDG-PET/CT has shown accuracy in detecting numerous primary cancers and their metastases including sarcomas, lymphomas, melanomas, and diverse adenocarcinomas and has been used to evaluate nearly all tumors associated with LFS.1518 For example, FDG-PET/CT scans have shown a greater than 70% sensitivity in detecting sarcomas and brain tumors, both hallmarks of LFS.2224 There have been few reports of PET/CT as a cancer screening tool.25,26

We performed a blinded central review of the FDG-PET/CT images of our cohort of 15 individuals and identified lesions that were characterized as likely, and later confirmed to be malignant, in 3 (20%). All 3 individuals were able to undergo potentially curative treatments. Clinical review led to additional procedures in one-third of individuals, which has important implications for subsequent study design. There have been no malignancies detected in the brief clinical follow-up of these patients (median, 8.5 months). The results of this pilot study are encouraging in this patient population given that treatable malignancies were detected in 20% of patients. A larger trial is needed to properly evaluate the clinical benefit and diagnostic performance of the screening in terms of sensitivity, specificity, and observer variability. The routine clinical use of FDG-PET/CT for screening patients with LFS may be less effective than in this controlled setting.

Imaging with FDG-PET/CT provides the opportunity to explore the whole body noninvasively. However, any radiation exposure should be carefully considered because individuals with LFS are at increased risk of subsequent primary malignant tumors.13,27 The radiation exposure from the single FDG-PET/CT scan performed in this trial (approximately 2.4 rem) is about equivalent to the sum of clinical chest, abdomen, pelvis, and head CT scans, and half the annual exposure limit for radiation workers. It is considered acceptable for currently approved clinical indications, which do not include screening, particularly in radiation-sensitive populations. Radiation doses from diagnostic procedures are typically 2 to 3 orders of magnitude smaller than the dose of therapeutic radiation with which secondary cancers have been linked. Nevertheless, there is growing concern for potential radiation risks of diagnostic procedures such as CT scans, particularly in the general population.2831

While the purpose of this study was to evaluate LFS screening with optimal FDG-PET image quality, the injected FDG dose could be reduced and the CT technique adjusted to include longer acquisitions, manual specification, or newer CT scanners with increased sensitivity without sacrificing quality.3235 A more definitive clinical trial evaluating FDG-PET/CT scanning in this population also should consider the appropriate scanning interval, age at initiation of screening, and possible alternate non–radiation-dependent techniques.

This study has several limitations. Because of the rarity of LFS, our sample size in this pilot study is small, and our convenience sample included cancer survivors free of disease for 5 years or more. The scans are incident, so they are more likely to identify prevalent occult disease. We identified a gastroesophageal junction tumor before it became symptomatic, but do not know whether this discovery will contribute to the patient's survival. Papillary thyroid cancers in individuals without LFS are often associated with very long survival; any potential differences in behavior have not been evaluated in patients with LFS.

In conclusion, FDG-PET/CT imaging has the potential to detect a wide variety of cancers at potentially curable stages. The use of an imaging technique that is effective in detecting cancer in the whole body with acceptable radiation exposure could potentially be considered for the screening of high-risk groups, such as LFS families, if confirmed in a larger study.

Corresponding Author: Judy E. Garber, MD, MPH, Dana-Farber Cancer Institute, 44 Binney St, SM 209, Boston, MA 02115 (judy_garber@dfci.harvard.edu).

Author Contributions: Dr Garber had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Masciari, Van den Abbeele, Diller, Yap, Schneider, Garber.

Acquisition of data: Masciari, Van den Abbeele, Rastarhuyeva, Yap, Digianni, Li, Fraumeni, Garber.

Analysis and interpretation of data: Masciari, Van den Abbeele, Diller, Rastarhuyeva, Yap, Syngal, Garber.

Drafting of the manuscript: Masciari, Van den Abbeele, Diller, Digianni.

Critical revision of the manuscript for important intellectual content: Van den Abbeele, Diller, Rastarhuyeva, Yap, Schneider, Li, Fraumeni, Syngal, Garber.

Statistical analysis: Masciari, Yap, Syngal.

Obtained funding: Diller, Li, Garber.

Administrative, technical, or material support: Van den Abbeele, Rastarhuyeva, Digianni, Fraumeni.

Study supervision: Van den Abbeele, Diller, Yap, Syngal, Garber.

Financial Disclosures: None reported.

Funding/Support: This research was supported by the Perini Family Survivor Center, the Swim Across America Foundation, and the Starr Foundation. Dr Masciari was supported by a Patterson Fellowship, a Charles A. King Trust and Bank of America Fellowship Co-trustee (Boston, Massachusetts), and by the Humane Society of the Commonwealth of Massachusetts Postdoctoral Research Fellowship. Dr Li is a Harry and Elsa Jiler American Cancer Society Clinical Research Professor.

Role of the Sponsor: The sponsors were not involved in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Additional Contributions: We thank Kate Brenton and Nina Cardoza (Department of Population Science, Dana-Farber Cancer Institute) and Madhavi Kamma (Department of Radiology, Dana-Farber Cancer Institute) for their administrative support. None received salary support or consulting fees for work on this study.

Li FP, Fraumeni JF Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. a familial syndrome?  Ann Intern Med. 1969;71(4):747-752
PubMed   |  Link to Article
Malkin D, Li FP, Strong LC,  et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.  Science. 1990;250(4985):1233-1238
PubMed   |  Link to Article
Varley JM, McGown G, Thorncroft M,  et al.  Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.  Cancer Res. 1997;57(15):3245-3252
PubMed
Garber JE, Goldstein AM, Kantor AF, Dreyfus MG, Fraumeni JF Jr, Li FP. Follow-up study of twenty-four families with Li-Fraumeni syndrome.  Cancer Res. 1991;51(22):6094-6097
PubMed
Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers.  Cancer Epidemiol Biomarkers Prev. 2001;10(2):83-87
PubMed
Wong P, Verselis SJ, Garber JE,  et al.  Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome.  Gastroenterology. 2006;130(1):73-79
PubMed   |  Link to Article
Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H. Tumors associated with p53 germline mutations: a synopsis of 91 families.  Am J Pathol. 1997;150(1):1-13
PubMed
Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP. Multiple primary cancers in families with Li-Fraumeni syndrome.  J Natl Cancer Inst. 1998;90(8):606-611
PubMed   |  Link to Article
Hwang SJ, Lozano G, Amos CI, Strong LC. Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.  Am J Hum Genet. 2003;72(4):975-983
PubMed   |  Link to Article
Birch JM, Hartley AL, Tricker KJ,  et al.  Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.  Cancer Res. 1994;54(5):1298-1304
PubMed
Eeles RA. Germline mutations in the TP53 gene.  Cancer Surv. 1995;25:101-124
PubMed
Varley JM, Evans DG, Birch JM. Li-Fraumeni syndrome–a molecular and clinical review.  Br J Cancer. 1997;76(1):1-14
PubMed   |  Link to Article
Li FP, Fraumeni JF Jr, Mulvihill JJ,  et al.  A cancer family syndrome in twenty-four kindreds.  Cancer Res. 1988;48(18):5358-5362
PubMed
Li FP, Garber JE, Friend SH,  et al.  Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals.  J Natl Cancer Inst. 1992;84(15):1156-1160
PubMed   |  Link to Article
Al-Sugair A, Coleman RE. Applications of PET in lung cancer.  Semin Nucl Med. 1998;28(4):303-319
PubMed   |  Link to Article
Oehr P, Ruhlmann J, Biersack HJ. FDG-PET in clinical oncology: review of the literature and report of one institution's experience.  J Investig Med. 1999;47(9):452-461
PubMed
Di Chiro G. Positron emission tomography using [18F] fluorodeoxyglucose in brain tumors: a powerful diagnostic and prognostic tool.  Invest Radiol. 1987;22(5):360-371
PubMed   |  Link to Article
Delbeke D. Oncological applications of FDG PET imaging: brain tumors, colorectal cancer, lymphoma and melanoma.  J Nucl Med. 1999;40(4):591-603
PubMed
Avril N, Rose CA, Schelling M,  et al.  Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.  J Clin Oncol. 2000;18(20):3495-3502
PubMed
Young H, Baum R, Cremerius U,  et al; European Organization for Research and Treatment of Cancer (EORTC) PET Study Group.  Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations.  Eur J Cancer. 1999;35(13):1773-1782
PubMed   |  Link to Article
Shankar LK, Hoffman JM, Bacharach S,  et al.  Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials.  J Nucl Med. 2006;47(6):1059-1066
PubMed
Ioannidis JP, Lau J. 18F-FDG PET for the diagnosis and grading of soft-tissue sarcoma: a meta-analysis.  J Nucl Med. 2003;44(5):717-724
PubMed
Folpe AL, Lyles RH, Sprouse JT, Conrad EU III, Eary JF. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma.  Clin Cancer Res. 2000;6(4):1279-1287
PubMed
Chao ST, Suh JH, Raja S, Lee SY, Barnett G. The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery.  Int J Cancer. 2001;96(3):191-197
PubMed   |  Link to Article
Yasuda S, Ide M, Fujii H,  et al.  Application of positron emission tomography imaging to cancer screening.  Br J Cancer. 2000;83(12):1607-1611
PubMed   |  Link to Article
Chen YK, Ding HJ, Su CT,  et al.  Application of PET and PET/CT imaging for cancer screening.  Anticancer Res. 2004;24(6):4103-4108
PubMed
Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP. Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome.  Int J Cancer. 2001;96(4):238-242
PubMed   |  Link to Article
Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation-induced fatal cancer from pediatric CT.  AJR Am J Roentgenol. 2001;176(2):289-296
PubMed   |  Link to Article
Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening.  Radiology. 2004;232(3):735-738
PubMed   |  Link to Article
Brenner DJ, Hall EJ. Computed tomography–an increasing source of radiation exposure.  N Engl J Med. 2007;357(22):2277-2284
PubMed   |  Link to Article
Chodick G, Ronckers CM, Shalev V, Ron E. Excess lifetime cancer mortality risk attributable to radiation exposure from computed tomography examinations in children.  Isr Med Assoc J. 2007;9(8):584-587
PubMed
Boone JM, Geraghty EM, Seibert JA, Wootton-Gorges SL. Dose reduction in pediatric CT: a rational approach.  Radiology. 2003;228(2):352-360
PubMed   |  Link to Article
Wilting JE, Zwartkruis A, van Leeuwen MS, Timmer J, Kamphuis AG, Feldberg M. A rational approach to dose reduction in CT: individualized scan protocols.  Eur Radiol. 2001;11(12):2627-2632
PubMed   |  Link to Article
Kalra MK, Maher MM, Toth TL,  et al.  Techniques and applications of automatic tube current modulation for CT.  Radiology. 2004;233(3):649-657
PubMed   |  Link to Article
American Association of Physicists in Medicine.  Measurement, reporting, and management of radiation dose in CT: AAPM Report No. 96. http://www.aapm.org/pubs/reports/RPT_96.pdf. Accessibility verified February 18, 2008

Figures

Place holder to copy figure label and caption
Figure 1. Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Images of an Individual With a Thyroid Cancer
Graphic Jump Location

Whole-body maximal intensity projection image (left) and axial transverse slices through the thyroid displayed as PET (top right), CT (middle right), and fused PET/CT images (bottom right) of a patient with Li-Fraumeni syndrome showing intense FDG uptake in the left lobe. The spiral CT scan was performed with a moderate dose to enable anatomical localization in addition to correction of photon attenuation. Arrowheads indicate the location of the nodule in the left lobe of the thyroid.

Place holder to copy figure label and caption
Figure 2. Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Images of an Individual With a Gastroesophageal Junction Cancer
Graphic Jump Location

Whole-body maximal intensity projection image (left) and axial transverse slices through the gastroesophageal junction displayed as PET (top right), CT (middle right), and fused PET/CT images (bottom right) of a patient with Li-Fraumeni syndrome showing focal FDG uptake in the gastroesophageal region. The spiral CT scan was performed with a moderate dose to enable anatomical localization in addition to correction of photon attenuation. Arrowheads indicate location of adenocarcinoma at the gastroesophageal junction.

Tables

Table Graphic Jump LocationTable. Features of Lesions Detected by Fluorodeoxyglucose F18–Positron Emission Tomography/Computed Tomography (FDG-PET/CT)

References

Li FP, Fraumeni JF Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. a familial syndrome?  Ann Intern Med. 1969;71(4):747-752
PubMed   |  Link to Article
Malkin D, Li FP, Strong LC,  et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.  Science. 1990;250(4985):1233-1238
PubMed   |  Link to Article
Varley JM, McGown G, Thorncroft M,  et al.  Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.  Cancer Res. 1997;57(15):3245-3252
PubMed
Garber JE, Goldstein AM, Kantor AF, Dreyfus MG, Fraumeni JF Jr, Li FP. Follow-up study of twenty-four families with Li-Fraumeni syndrome.  Cancer Res. 1991;51(22):6094-6097
PubMed
Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers.  Cancer Epidemiol Biomarkers Prev. 2001;10(2):83-87
PubMed
Wong P, Verselis SJ, Garber JE,  et al.  Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome.  Gastroenterology. 2006;130(1):73-79
PubMed   |  Link to Article
Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H. Tumors associated with p53 germline mutations: a synopsis of 91 families.  Am J Pathol. 1997;150(1):1-13
PubMed
Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP. Multiple primary cancers in families with Li-Fraumeni syndrome.  J Natl Cancer Inst. 1998;90(8):606-611
PubMed   |  Link to Article
Hwang SJ, Lozano G, Amos CI, Strong LC. Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.  Am J Hum Genet. 2003;72(4):975-983
PubMed   |  Link to Article
Birch JM, Hartley AL, Tricker KJ,  et al.  Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.  Cancer Res. 1994;54(5):1298-1304
PubMed
Eeles RA. Germline mutations in the TP53 gene.  Cancer Surv. 1995;25:101-124
PubMed
Varley JM, Evans DG, Birch JM. Li-Fraumeni syndrome–a molecular and clinical review.  Br J Cancer. 1997;76(1):1-14
PubMed   |  Link to Article
Li FP, Fraumeni JF Jr, Mulvihill JJ,  et al.  A cancer family syndrome in twenty-four kindreds.  Cancer Res. 1988;48(18):5358-5362
PubMed
Li FP, Garber JE, Friend SH,  et al.  Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals.  J Natl Cancer Inst. 1992;84(15):1156-1160
PubMed   |  Link to Article
Al-Sugair A, Coleman RE. Applications of PET in lung cancer.  Semin Nucl Med. 1998;28(4):303-319
PubMed   |  Link to Article
Oehr P, Ruhlmann J, Biersack HJ. FDG-PET in clinical oncology: review of the literature and report of one institution's experience.  J Investig Med. 1999;47(9):452-461
PubMed
Di Chiro G. Positron emission tomography using [18F] fluorodeoxyglucose in brain tumors: a powerful diagnostic and prognostic tool.  Invest Radiol. 1987;22(5):360-371
PubMed   |  Link to Article
Delbeke D. Oncological applications of FDG PET imaging: brain tumors, colorectal cancer, lymphoma and melanoma.  J Nucl Med. 1999;40(4):591-603
PubMed
Avril N, Rose CA, Schelling M,  et al.  Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.  J Clin Oncol. 2000;18(20):3495-3502
PubMed
Young H, Baum R, Cremerius U,  et al; European Organization for Research and Treatment of Cancer (EORTC) PET Study Group.  Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations.  Eur J Cancer. 1999;35(13):1773-1782
PubMed   |  Link to Article
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