|Year : 2003 | Volume
| Issue : 3 | Page : 87-100
Positron emission tomography imaging in evaluation of cancer patients.
R Kumar, P Bhargava, MF Bozkurt, H Zhuang, S Potenta, A Alavi
Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, 110 Donner Bldg., 3400 Spruce Street, Philadelphia, PA 19104, USA
Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, 110 Donner Bldg., 3400 Spruce Street, Philadelphia, PA 19104
Source of Support: None, Conflict of Interest: None
Positron emission tomography (PET) is a diagnostic imaging technique that has progressed rapidly from being a research technique in laboratories to a routine clinical imaging modality. The most widely used radiotracer in PET is Fluorine18-fluorodeoxyglucose (F18-FDG), which is an analogue of glucose. The FDG uptake in cells is directly proportional to glucose metabolism of cells. Since glucose metabolism is increased many fold in malignant tumors PET has a high sensitivity and a high negative predictive value. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy, and management of lung cancer, colonic cancer, lymphoma, melanoma, esophageal cancer, head and neck cancer and breast cancer. Other indications of PET like bone tumor, ovarian cancer and cancer of unknown primary (CUP) has also been discussed in brief. The aim of this review article is to review the clinical applications of PET in various malignancies and only limited number of important studies will be discussed for this effort.
Keywords: Positron emission tomography, Fluorodeoxyglucose, Lymphoma, colonic cancer, Lung nodule and lung cancer, Breast cancer, Head and neck cancer, Ovarian cancer, Melanoma, Gastric and esophageal cancer.
|How to cite this article:|
Kumar R, Bhargava P, Bozkurt M F, Zhuang H, Potenta S, Alavi A. Positron emission tomography imaging in evaluation of cancer patients. Indian J Cancer 2003;40:87-100
|How to cite this URL:|
Kumar R, Bhargava P, Bozkurt M F, Zhuang H, Potenta S, Alavi A. Positron emission tomography imaging in evaluation of cancer patients. Indian J Cancer [serial online] 2003 [cited 2019 Sep 19];40:87-100. Available from: http://www.indianjcancer.com/text.asp?2003/40/3/87/13063
| » Introduction|| |
Positron emission tomography (PET) is an advanced diagnostic imaging technique that is used for diagnosis, staging and restaging after treatment or recurrence of various cancers. This technique exploits the increased metabolism of glucose in malignant viable cells. 2-[fluorine18-fluoro-2-deoxy-D-glucose (FDG) which is an analogue of glucose detects the difference in glucose metabolism. Like glucose, FDG is transported into tumor cells, by means of glucose transporter protein and subsequently it is phosphorylated by an enzyme hexokinase to FDG-6-phosphate., As FDG-6-phosphate is not a substrate for glucose-6-phosphate isomerase (the next step in glycolysis), it is biochemically trapped within the cell. This process of metabolic trapping in cell constitutes the basis for imaging of distribution of tracer with PET. Since there is many fold increase in glucose metabolism in malignant tumors as compared to normal, it is easy to detect this difference in metabolism using PET. Therefore PET has high sensitivity and high negative predictive value as compared to conventional morphological modalities like computed tomography (CT), Ultrasonography (USG), magnetic resonance imaging (MRI), which use size as the only or major criterion to distinguish between benign and malignant disease in lymph nodes., PET has well-established role in initial staging, monitoring the response to the therapy, and management of various cancers [Table - 1]. The list of reimbursable indications for FDG PET is growing, as more research is being done.
| » Solitary Pulmonary Nodules|| |
The incidence of malignancy in solitary pulmonary nodules (SPN) ranges from 10% to 70% and there is still controversy regarding optimal management of solitary pulmonary nodules., CT is useful mainly in the correct localization of SPNs and it can also differentiate nearly one-third of SPNs as malignant or benign in etiology, based on image characteristics.,
FDG-PET has been successfully used as a non-invasive diagnostic test for SPNs in order to differentiate benign lesions from malignancy. In the visual interpretation of FDG PET images, intense uptake of FDG at approximately at 1-hour images after injection is considered 'positive' [Figure - 1]. Recent studies have shown better results with delayed images taken several hours after injection (dual time point imaging), along with routine 1-hour imaging protocol.,, These studies concluded that malignant nodules show increasing FDG uptake by time, while pulmonary nodules of benign origin have a declining pattern of uptake with time. FDG uptake in a lesion can be quantitated by calculating its SUV (standardized uptake value). In general, SUV over 2.5 is considered as characteristic of malignancy, whereas in some studies SUV over 2 has also been used as a threshold value.
The importance of PET for the differential diagnosis of SPNs has been shown in many studies.,,, A meta-analysis study in which 450 SPNs were included concluded that the mean sensitivity and specificity for detecting malignancy were 93.9% and 85.8% respectively. The studies that investigated the role of FDG-PET imaging in the differential diagnosis of SPNs reported a wide variation in their specificity. The cause of this wide variation may be attributed to the prevalence of granulomatous diseases like tuberculosis, histoplasmosis or coccidioidomycosis which are varied widely according to the geographical localization.
FDG-PET has very important role in the management of patients with SPNs, but use of FDG-PET for this purpose warrants a high negative predictive value, which is related to the pre-test probability of cancer and to the sensitivity and specificity of FDG-PET method. Gambhir et al reported that FDG-PET imaging is an appropriate method for detection of malignancy in SPNs only for patients with 50% or lower pre-test probability of cancer, as determined by factors like lesion size, age, smoking history. If the patient has a higher pre-test probability for cancer, histologic diagnosis is needed regardless of FDG-PET result, since the post-test probability of cancer after a negative PET study may be as high as 10%. It is recommended that patients with a negative PET study and a high pre test probability should be followed up by clinical assessment and imaging studies, since a little risk of false negative result remains. For these patients a follow-up of 6-12 month intervals for monitoring the possible increase in the lesion size will be an indication for histologic diagnosis.,
FDG-PET has been approved differential diagnosis of solitary pulmonary nodules. Since FDG-PET has a high diagnostic accuracy, it has been incorporated into the routine diagnostic procedures for differentiation of benign nodules from malignant ones.
| » Lung Cancer|| |
The diagnosis of lung cancer still remains to be a problematic issue. Morphological imaging methods such as CT of chest can detect a nodule or mass in the lungs but cannot differentiate benign from malignant lesions. Because of this, accurate diagnosis of lung cancer can only be established with invasive diagnostic procedures, that are associated with complications and that have a morbidity rate of 1-10%.
| » Initial Staging|| |
In the literature the majority of FDG PET studies for lung cancer have been done in non-small cell lung cancer (NSLC) patients, in whom regional and distant involvement of disease will change staging and guide the therapeutic approach. In general, CT is the method of choice to define the extent of the primary tumor and to assess the tumour involvement of the pleural surfaces and the thoracic wall. For some patients, MRI can be used as an additional imaging modality, especially to evaluate the relationship of tumor to the heart and large vessels., The main limitation of CT/MRI is using a size criterion of 1 cm for the diagnosis of tumour involvement. For this reason, CT cannot report any lymph node with tumor involvement if it is smaller than 1 cm in diameter. In contrast, all of the lymph nodes larger than 1 cm in diameter will be defined as tumor involvement and will mislead the therapeutic management. Since FDG PET imaging depends on the criterion of increased metabolism, but not size, it can be used successfully in order to differentiate malignant nodes from the others [Figure - 2]. In the literature there are some studies in which the accuracy of CT and FDG PET have been compared to each other., Pieterman et al reported that the sensitivity and specificity of PET and CT for the evaluation of mediastinal nodal involvement were 91% and 86% for PET; and 75% and 66% for CT respectively. Dwamena et al in their meta-analysis of staging lung cancer by PET and CT concluded that FDG PET was significantly more accurate than CT and reported the sensitivity and specificity values of 79% and 91% for PET and 60% and 77% for CT respectively. Several authors reported that correlation of anatomic (CT, MRI) imaging with functional (PET) imaging or PET/CT fusion imaging may also be useful for the further improvement of determining the patients with nodal disease.,
PET also can detect distant metastases effectively.,,, FDG PET can detect distant metastases that are unsuspected after conventional staging in 10-14% of lung cancer patients. FDG PET is an accurate imaging modality in order to rule out metastasis in cases of false positive or indeterminate anatomical imaging findings. FDG PET has also a particularly important role for detecting adrenal metastases in lung cancer patients. Up to 20% of lung cancer patients are found to have an adrenal mass by CT, without necessarily confirming metastasis. It has been reported that FDG PET can eliminate the need for biopsy of enlarged adrenal glands in lung cancer patients.,
| » Monitoring Treatment Response|| |
Anatomical imaging methods use the criterion of tumor shrinkage in order to define a good therapy response but this criteria may not be the best indicator of response to therapy, since fibrotic tissue secondary to therapy may give the same image pattern as a non or partially responding mass. FDG PET imaging, which uses metabolic criterion, is a more accurate method to differentiate tumor from scar tissue. Bury et al reported that FDG PET was more sensitive and equally specific compared to other imaging modalities for detection of residual disease or recurrence after surgery or radiotherapy. In the literature there are also some other studies reporting the higher accuracy of FDG PET for differentiating treatment changes from recurrent disease compared to CT., Also a cutoff SUV of 2.5 may be accepted as accurate in differentiating tumor from benign post therapeutic changes.
| » Recurrence/Prognosis|| |
Normalization of FDG uptake following the therapy has been reported to be a good prognostic sign., Hebert et al showed that all of the patients in their study with normal FDG uptake after therapy were alive at 2 years after treatment, while 50% of patients with post therapeutic residual FDG uptake had died within the same 2 year period. In the literature some studies reported an independent prognostic value of FDG uptake in lung cancer, so that patients with SUV of more than 7 or 10 had shorter survival compared to the ones with SUV below these thresholds.,
FDG-PET imaging has been approved for the diagnosis, initial staging and restaging of only non-small cell lung cancer. Although there are some studies in the literature that provides convincing evidence for the use of FDG-PET for small cell lung cancer, further studies are still warranted.
| » Colorectal Carcinoma|| |
Colorectal carcinoma is the third most common malignancy in men, and the second in women and is the fourth leading cause of all cancer deaths., If the disease can be diagnosed in the early stages, the surgical treatment is almost curative with minimal morbidity and mortality rates. Only 70-80% of patients can undergo curative resection at presentation and their overall 5-year survival is less than 60%.
| » Initial Staging|| |
Although the sensitivity of FDG PET for the preoperative diagnosis of colorectal carcinoma is high, it has no important role in practice, since surgical diagnosis and staging will be needed for all patients. Abdel-Nabi et al reported that FDG PET imaging was successful for the identification of all primary lesions in 48 patients. However both FDG PET and CT missed approximately 70% of nodal metastases. But FDG PET was found to be superior to CT for the identification of liver metastases with a sensitivity and specificity of 88% and 100% respectively versus 38% and 97% respectively for CT. The common false positive findings of FDG PET were fistulas, abscesses, diverticulitis and less frequently adenomas.
| » Monitoring Treatment Response|| |
Haberkorn et al reported the efficacy of FDG PET to monitor the response to radiation therapy. In this study, statistically significant reduction in FDG uptake of tumors following radiation therapy was seen only in 50% of patients, and reduction of FDG uptake correlated with satisfactory palliative results. FDG PET was also found to be more sensitive in detection of recurrent disease compared to serum CEA measurement. Vitola et al studied the effects of regional chemoembolization therapy using FDG uptake as a criterion and found that decreased FDG uptake correlated with response while presence of residual uptake was used to guide further regional therapy.
In their study Findlay et al assessed the metabolic characteristics of colorectal cancer liver metastases in 18 patients using both FDG PET and CT before and during the first month of 5-Fluorouracil chemotherapy, regarding to the changes in size and FDG uptake of lesions. They performed FDG-PET studies before treatment, after 1-2 week and 4-5 week of treatment. They concluded that FDG PET was accurate for differentiation of responders from non-responders, both on lesion-by-lesion or patient-by-patient analysis. Tumor response was associated with lower tumor-to-liver uptake ratios at 1-2 week and 4-5 week FDG PET studies, as well as lower SUVs after 4-5 weeks of therapy.
| » Recurrence/Prognosis|| |
Colorectal cancer will recur in approximately 30% of patients within 2 years, and in 25% of these patients the recurrence of disease will be isolated to one site, mostly liver and surgery may serve as a potentially curable therapeutic option. The presence of extrahepatic metastases is considered to be a contraindication to lesion excision, and also the number and the size of hepatic metastases adversely affect prognosis. FDG PET has an important role to detect extrahepatic metastases and plays a vital role in selection of patients who may benefit from partial hepatectomy.
In general, serial serum CEA levels are used for recurrence monitoring, but when a high serum level of CEA is encountered, imaging will be necessary to localize the site of possible recurrence. CT is usually incapable of differentiating post surgical changes from recurrence and also it commonly misses extrahepatic abdominal metastases and fails to detect hepatic metastases in 7% patients as well. Functional imaging with FDG PET can be successfully used to identify the metabolic characteristics of the lesions, which are equivocal or even not seen by CT, and FDG PET can define the recurrence as a complementary test [Figure - 3]. Valk et al in their study compared the sensitivity and specificity of FDG PET and CT side-by-side. According to their study, FDG PET was found to be more sensitive for all sites except the lung, where both imaging techniques had equivalent sensitivities. They also reported that one third of FDG positive lesions in the abdomen, pelvis and retroperitoneum were negative on CT. Other studies showed that whole-body FDG PET imaging is especially useful for defining distant metastases, such as abdominal nodal involvement and lung metastases., Also PET is accurately capable of differentiating post surgical changes from recurrence, in contrast to CT, the accuracy of PET in this regard ranges from 90-100% where accuracy values for CT are reported to be 48-65%.
FDG-PET has been approved for diagnosis, initial staging and restaging of colorectal cancer. However FDG-PET is not practically preferred for the preoperative diagnosis of colorectal cancer. Currently the main indication of FDG-PET for colorectal cancer is the assessment of regional and distant metastasis and mainly the identification of recurrence in patients with rising CEA levels when conventional imaging modalities fail.
| » Breast Cancer|| |
Breast cancer is the most common malignancy in women in most of countries. The use of F18-FDG PET in breast carcinoma has been evaluated in the initial staging, monitoring the response to chemotherapy and determination of metastatic disease.
| » Initial Staging|| |
In the last several years, there have been intense efforts to apply various imaging modalities to improve the detection, diagnosis and local staging of breast cancer. Wahl et al and Bruce et al detected all primary tumours using PET in 10 and 15 patients respectively., FDG PET plays an important role in differentiation between benign and malignant tumours.,, The sensitivity of PET for breast cancer varies between 68% and 100%.,,,, A study by Schirrmeister et al showed that whole body FDG PET is as accurate as panel of imaging modalities currently employed and significantly more accurate in detecting multifocal disease, lymph node involvement and distant metastasis [Figure - 4]. Same group evaluated relation of FDG uptake and biological and clinical prognostic parameters and found that FDG uptake was significantly higher in ductal than in lobular cancer and FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining.
Metastasis to axillary lymph nodes is one of the most important prognostic factors in breast cancer patients. There is no effective non-invasive modality to know the involvement of axillary status of lymph nodes except axillary dissection and sentinel lymph node sampling. Cripa F et al showed overall diagnostic accuracy of 86%. The accuracy was very high (95%) in N1a patients. The sensitivity of FDG PET in detection of axillary lymph node metastasis varies from 79-100%.,, FGD PET can miss micrometastases in lymph nodes as there are fewer cells, which may or may not have increased glucose metabolism to be detected. Axillary lymph nodes dissection or sentinel lymph node samplings are the best method to know the axillary lymph node involvement. 
| » Monitoring Treatment Response|| |
Multi-modality therapy beginning with neoadjuvant chemotherapy (NACT) is the standard of care for the patients with locally advanced breast cancer (LABC). NACT is associated with a good response rate in more than 70% of the patients including a complete pathologic remission rate of about 10% to 15%., Following successful induction chemotherapy, a variety of options for local treatment have been investigated. These include surgery alone, surgery and radiotherapy, and radiotherapy alone., However, unless a reliable method is available to assess the residual tumor after neoadjuvant chemotherapy, decisions on the need and the extent of subsequent surgical management would be difficult.
FDG PET has been reported to detect metabolic changes in breast cancer as early as 8 days after initiation of chemotherapy. In the literature there are several studies, which differentiated responder from non-responder after first course of therapy using FDG PET imaging.,, Responders were correctly identified with sensitivity of 90% and 100% and specificity of 74% and 85% by Schelling et al and Smith et al respectively after first course of chemotherapy., Bassa et al found that FDG PET was useful in evaluating response to chemotherapy for primary LABC. They showed a good correlation of persistent FDG uptake after completion chemotherapy and poor prognosis. In a recent study, the factors influencing the response to chemotherapy in LABC patients were investigated using FDG and O15-water. The authors hypothesized that low tumor perfusion and high FDG metabolism correlated with the poor response to chemotherapy.
Vranjesvic et al predicted the response to chemotherapy in 61 patients using FDG PET and conventional imaging (CT/MRI/USG). PET was more accurate than combined conventional imaging modalities with positive and negative predictive values of 93% and 84% respectively for FDG PET versus 85% and 59% respectively for conventional imaging modalities. The accuracy was 90% and 75% for FDG PET and conventional imaging modalities respectively.
| » Recurrence/Prognosis|| |
Locoregional and distant metastasis occurs in up to 35% of patients within 10 year of initial surgery of breast cancer. Early detection of recurrent or metastasis may be beneficial in instituting local or systemic treatment to prevent tumor related symptoms., CT and other morphologically oriented images reflect mainly morphological changes and nodular size is the only or major critical criterion of malignancy. Whole body FDG PET has emerged as a sensitive and noninvasive technique in management of breast cancer. 
Gallowitsch et al in a retrospective analysis in 62 patients, showed sensitivity, specificity, PPV, NPV and accuracy of 97%, 82%, 87%, 96% and 90% for FDG PET and 84%, 60%, 73%, 75% and 74% for conventional imaging. On lesion basis, significantly more lymph node vs  and fewer bone metastases vs  were detected by using FDG compared with conventional imaging. Kamel et al analysed the role of FDG PET 60 patients for detecting relapse. The overall sensitivity, specificity and accuracy were 89%, 84% and 87% for locoregional and 100%, 97% and 98% for distant metastasis. The author also concluded that FDG PET was more sensitive than the serum tumor marker CA 15-3 in detecting breast cancer relapse. Eubank et al compared FDG PET and CT in 73 recurrent/metastatic breast cancer patients for evaluation of mediastinal and internal mammary lymph nodes metastases. In 33 patients amenable to follow-up CT or biopsy, FDG PET revealed a superior detection rate of 85% compared to CT 54%, when prospectively interpreted.,
FDG PET has shown a variable degree of sensitivity and specificity in detecting bone metastasis. Moon et al reported a sensitivity of 93% and specificity of 79% with FDG PET in detecting recurrent or metastatic disease. FDG PET had many false negative results, particularly sclerotic lesions. Gallowwitsch et al and Kao et al had better specificity but lower sensitivity for detecting bone metastasis., Non-detectable lesions on FDG PET were sclerotic or mixed sclerotic/osteolytic radiologically. PET has also limited role in detecting bone metastasis in skull due to high uptake in brain. The combination of FDG PET scan and bone scan can be done for better sensitivity and specificity for bone metastases in breast cancer patients.
Currently, FDG-PET that have been approved for initial staging in patients with distant metastases, restaging in patients with locoregional and distant metastases and monitoring response to therapy in patients with locally advanced and metastatic disease. However, evaluation of regional lymph nodes is still not covered, since sentinel lymph node detection is the method of choice for this purpose.
| » Lymphoma|| |
Presently, most of the management decisions in lymphoma patients are based on CT scan for initial staging and follow-up, measurements of specific blood indices such as the ESR, absolute lymphocyte counts and serum LDH. However CT can only define anatomy and is insufficient for depiction of small volume of tumors in normal sized structures as size is the main diagnostic criterion of malignancy. It has also limited role in evaluating response to treatment, as most of the lesions does not shrink, especially fibrotic lymph nodes. Metabolic imaging with FDG PET has emerged as a powerful imaging modality for diagnosis, staging, and treatment monitoring of lymphoma patients.
| » Initial Staging|| |
Diagnosis and staging mainly depend on history, clinical examination, laboratory data, imaging with CT and/or MRI and Gallium-67. The accuracy of FDG PET is better than CT/MRI and Gallium scintigraphy., Moog et al studied 60 consecutive patients with HD and NHL, FDG PET found 25 additional lesions, while CT found 6 additional lesions of which three were false positive. Stumpe at al had similar experience when accuracy of FDG PET was compared with CT. There was no significant difference in sensitivity but the specificity was 96% for HD and 100% for NHL using PET, while the corresponding values were 41% and 67% for CT. Cremerius et al and Zinzani et al both showed a sensitivity of 100% and specificity of 17% for CT while sensitivity were 100% for both and specificity were 92% and 96% for PET., Recently, Sasaki et al showed a specificity of 99% for CT and PET but sensitivity was 65% and 92% for CT and PET. These studies show that there is large variation in sensitivity and specificity of CT, whereas these figures are not that variable with FDG PET [Figure - 5]. Another major advantage of FDG PET is that, it is a whole body imaging method.
A number of publications have posed the clinically relevant question of how FDG-PET impact on staging on patient management. PET modified therapy in 25% of all lymphoma patients. Apparently, 23% of patients were assigned a different stage by FDG PET imaging compared with conventional imaging.,.
| » Monitoring Treatment Response|| |
Several studies have shown the effectiveness of FDG PET in post treatment of lymphoma and found that PET has high predictive value for the differentiation between active tumor and fibrosis [Figure - 6]. Jerusalem et al compared the prognostic role of FDG PET and CT after first line treatment in 54 NHL/HD patients. FDG PET had higher diagnostic and prognostic value than CT (positive predictive value 100% vs 42%). The 1-year PFS survival was 86% in PET -Ve patients as compared to 0% in PET +Ve patients. Mikhaeel et al compared FDG PET with CT as prognostic indicator in treatment of aggressive NHL. The relapse was 17 % for PET -Ve and 100% for PET +Ve compared with 25% and 41% for negative and positive CT respectively. The PFS was 83% for PET -Ve as compare to 0% for PET +Ve group. Recently, Juweid et al also showed PPV and NPV for FDG PET for 1-year PFS were 92% and 88% respectively, compared with 47% and 85% for CT in patients with NHL.
Spaepen et al evaluated 60 patients of HD who had FDG PET at the end of first line treatment with or with out residual mass. The 2-year DFS was 4% for PET +Ve and 85% for PET -Ve group. Mikhaeel et al confirmed these findings in 65 HD patients, with a 1-year PFS of 0% vs 93%.
FDG PET also has important role in prognostication patients even after first cycle of chemotherapy. Kostakoglu et al recently compared FDG scan done after first cycle of chemotherapy and after completion of chemotherapy. PET had greater sensitivity and PPV after the first cycle (82% vs 45% and 90% vs 83%).
| » Recurrence/Prognosis|| |
Approximately two third of patients with HD present with mass lesion in location of a previous tumor manifestation, but, only about 20% of patients ultimately relapse., Similarly, in patients with NHL 50% present with mass lesion and only 25% relapse in high grade NHL., A single CT or other morphological imaging cannot differentiate between fibrosis and recurrence. Since FDG uptake depends upon the metabolic state of the lesion in question and not on the size of the lesion, FDG PET provides solution to this diagnostic dilemma. Though Gallium scintigraphy has proved useful in patients with recurrent disease, it is less sensitive in intraabdominal and low-grade lymphoma.,
Cremerius et al reported sensitivity 88% and a specificity of 83% for detection of residual disease for FDG PET. The corresponding values for CT were 84% and 31% respectively. Recently, a study by Mikosch et al compared PET with CT/US in detecting recurrence and reported a sensitivity of 91%, specificity of 81%, PPV of 79%, PPV of 92% and accuracy of 85%. The similar values 88%, 35%, 48%, 81% and 56% respectively for CT/US.
The present approved indications for FDG-PET are diagnosis, initial staging and restaging of Hodgkin's disease and non-Hodgkin lymphoma. Based on the present literature data, FDG-PET has been found to have high diagnostic accuracy for staging and restaging lymphoma and it can provide better prognostic information compared to anatomical imaging modalities.
| » Head and Neck Cancer|| |
The presence of lymph node spread of head and neck tumours is associated with substantially worse prognosis. Accurate pre therapy lymph node staging is essential for planning surgical or other management strategy. Conventional imaging like CT/MRI detects only fewer than 50% of involved nodes due to their dependence on size criteria and many times result in unnecessary neck surgery. Lymph node staging in these patients with FDG PET is more accurate than conventional imaging modalities.,,, The sensitivity and specificity of FDG PET varies 71% to 91% and 88% to 100% in detecting metastatic lymph nodes. Adams et al and Kau et al reported sensitivity and specificity 90% and 94% for FDG PET, 80% and 85% for CT and 88% and 79% for MRI respectively., FDG PET can demonstrate up to 30% of previously undetected primary head and neck tumours [Figure - 7].
After radiation therapy and surgery, distortion of normal anatomic structures limits the ability of MRI and CT to demonstrate residual or recurrent disease. The FDG PET has comparable sensitivity of 88-100% vs 72-92% and better specificity of 75-100% vs 50-57% with CT and MRI in detecting recurrence at primary site.,, FDG PET is also more sensitive and specific in detecting residual and recurrent lymph node metastasis., The accuracy of FDG PET was 85% as compared to 42% for CT in differentiating recurrent laryngeal cancer from post radiation soft tissue changes. In identifying the response to treatment PET has very important role. A study by Lowe et al showed mean reduction of 82% FDG activity in patients who achieved complete remission compared to 34% reduction in FDG activity in those who had recurrent disease. The sensitivity and specificity of FDG PET for residual cancer 1-2 week after treatment were 90% and 83% respectively in patients with head and neck cancer. Recently, Brun et al predicted the therapy outcome using FDG PET in 47 head and neck cancers patients. They concluded that FDG PET in early phase of treatment of head and neck cancer is associated with tumour response, survival and locoregional control.
At present FDG-PET has been approved for the diagnosis, initial staging and restaging of head and cancer, excluding the neoplasm's of the central nervous system and thyroid gland. Recent advances in imaging technology, such as the routine use of devices like PET/CT will probably increase the use of PET for head and neck cancer patients.
| » Malignant Melanoma|| |
Many researchers evaluated the role of FDG PET for staging of melanoma [Figure - 8]. The accuracy of PET in detecting metastatic melanoma has ranged from 81-100%. But the sensitivity decreases when the tumour size less than 5 mm. Damian et al in largest series of 100 patients demonstrated a sensitivity of 93%. They also showed that FDG PET detected disease up to 6 months earlier than conventional imaging modalities and altered management in 22% patients. FDG PET can miss small tumours and micrometastases, in such cases sentinel lymph node biopsy using gamma probe is ideal procedure, which has sensitivity of more than 94% and specificity of 100%. FDG PET has better sensitivity of 94% and specificity of 94% as compared to CT, which has 55% and 84% respectively in detecting metastatic melanoma., FDG PET is more accurate than conventional imaging in restaging and follow-up of patients with melanoma, it has sensitivity of 92% vs 57.7% and a specificity of 94% vs 45% respectively.
FDG-PET has been approved for the diagnosis, initial staging and restaging of malignant melanoma patients. However, evaluation of regional lymph nodes is still not covered, since sentinel lymph node detection is the method of choice for this purpose.
| » Gastric and Esophageal Cancer|| |
FDG PET is sensitive for detection of primary gastric/esophageal squamous cell as well as adenocarcinoma.,,,, Although, the detection of primary tumour has been reported to be excellent, the identification of regional nodal metastases has been restricted due to involvement of small volume of disease in some of lymph node. But still FDG is more specific than CT and endoscopic US for locoregional lymph node metastasis.,,, However, biopsy remains the gold standard for detecting lympg node involvement. FDG PET changed the management in 22% cases.,, Therefore PET is reliable in differentiating resectable from non-resectable disease and avoids many unnecessary surgeries [Figure - 9].
FDG PET is more accurate than conventional imaging with CT and US in evaluating response to radiation therapy and chemotherapy. A recent study showed FDG PET is very sensitive in identifying responders to neoadjuvant therapy. The responders have significant change in FDG uptake as compared to non-responders after treatment.
FDG-PET has been recently approved for the diagnosis, initial staging and restaging of esophageal cancer. Also there are some encouraging reports regarding the importance of FDG-PET for therapy response monitoring in esophageal cancer. As these studies increase in number, PET will probably be used more in routine practice.
| » Bone Tumours|| |
Multiple myeloma and osteosarcoma are most common malignant primary bone tumours. In multiple myeloma bone scan shows marrow involvement indirectly by imaging cortical bone osteoblastic reaction to the marrow tumour while FDG PET shows marrow involvement directly. Jadvar et al concluded that FDG PET could detect early marrow involvement as compared to bone scan and other conventional imaging. PET is also useful in assessing response to treatment. The other studies in this regard also showed encouraging results in demonstrating the active site of tumour involvement in planning the mode of treatment.,,
In osteosarcoma, degree of FDG uptake in tumour has good correlation with histological grading or tumour aggressiveness., Eary et al reported that baseline SUV can predict out come in a better way than conventional grading in meta-analysis of 209 patients. FDG PET scan also guides biopsy to the most active tumor metabolic site. In osteosarcoma, since lymph node metastases are very rare the experience in detecting lymph node metastases is limited. Lucas et al showed that FDG detected more lesions as compared to CT and MRI. Recently, Brenner et al in their review of PET studies in osteosarcoma concluded that FDG PET is useful in predicting outcome as well as tumor response in neoadjuvant chemotherapy, differentiating postoperative changes from residual tumor tissue or local relapse and for detecting distant metastases.
The use of FDG-PET for bone tumors is not a Medicare approved oncologic indication yet.
| » Ovarian Cancer|| |
Ovarian carcinoma is spread through out pelvis in about two third of all patients at the time of presentation. Accurate staging is very important for proper management, especially in patients with raised serum CA-125. FDG PET has shown high sensitivity and specificity as compared to conventional imaging modalities in detecting lymph node metastases, however like other imaging modalities, it has limited role in micrometastases and very small lesions [Figure - 10].,, Surgical biopsy staging remains gold standard to know small lymph nodes metastases and micrometastases.
Although FDG-PET has not yet been approved by the Health Care Finance Administration for Medicare reimbursement for ovarian cancer, it may be used depending on the patient's insurance. More studies regarding the importance and necessity of PET imaging for ovarian cancer is still warranted.
| » Cancer of Unknown Primary (CUP)|| |
Many studies have been published in the literature to evaluate the role of PET in patients with cancer of unknown primary.,, However, there are very few studies to date, which have analyzed the impact of PET results on therapeutic management. Rades et al detected the primary site in 18 of 42 patients using PET, all these patients had localized cancer of unknown origin by using conventional staging procedures. PET was positive for disseminated diseases in 38% patients. In 69% patients PET results influenced the selection of the definitive treatment.
| » Conclusions|| |
Positron emission tomography is an advanced diagnostic functional imaging technique, which can not only detect but also quantify disease processes in vivo non-invasively. The principle of PET is to detect altered metabolism of disease processes and not the altered anatomy. 18F-FDG is the most widely used radiotracer in oncology. Since glucose metabolism is increased many fold in malignant tumors as compared to normal cells, PET has high sensitivity and high negative predictive value. It has a well-established role in initial staging, monitoring response to the therapy, and management of many types of cancer, including lung cancer, colon cancer, lymphoma, melanoma, esophageal cancer, head and neck cancer, and breast cancer.
| » Acknowledgements|| |
We are thankful to International Union Against Cancer (UICC), Geneva, Switzerland for financial support (ACSBI fellowship) to Dr. Rakesh Kumar.
| » References|| |
|1.||McGowan KM, Long SD, Pekala PH. Glucose transporter gene expression: regulation of transcription and mRNA stability. Pharmacol Ther 1995;66:465-505. [PUBMED] [FULLTEXT]|
|2.||Wahl RL. Targeting glucose transporters for tumor imaging: "sweet" idea, "sour" result. J Nucl Med 1996;37:1038-41. |
|3.||Matthies A, Schuster SJ, Alavi A. Staging and monitoring response to treatment in primary non-Hodgkin's lymphoma of bone marrow using (18)F-fluorodeoxyglucose positron emission tomography. Clin Lymphoma 2001;1:303-6. [PUBMED] [FULLTEXT]|
|4.||De Wit M, Bumann D, Beyer W, Herbst K, Clausen M, Hossfeld DK. Whole-body positron emission tomography (PET) for diagnosis of residual mass in patients with lymphoma. Ann Oncol 1997;8:57-60. |
|5.||Siegelman SS, Khouri NF, Leo FP, fishman EK, Braverman RM, Zerhouni EA. Solitary pulmonary nodules: CT assessment. Radiology 1986;160:307-12. |
|6.||Khouri NF, Meziane MA, Zerhouni EA, Fishman EK, Siegelman SS. The solitary pulmonary nodule. Assessment, diagnosis, and management. Chest. 1987;91:128-33. |
|7.||Ost D, Fein A. Evaluation and management of the solitary pulmonary nodule. Am J Respir Crit Care Med 2000;162:782-7 |
|8.||Ward HB, Pliego M, Diefenthal HC, Humphrey EW. The impact of phantom CT scanning on surgery for the solitary pulmonary nodule. Surgery 1989;106:734-8. |
|9.||Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med 2002;43:871-5. |
|10.||Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 2001;42:1412-7. |
|11.||Hustinx R, Dolin RJ, Benard F, Bhatnagar A, Chakraborty D, Smith RJ, et al. Impact of attenuation correction on the accuracy of FDG-PET in patients with abdominal tumors: a free-response ROC analysis. Eur J Nucl Med 2000;27:1365-71. |
|12.||Knight SB, Delbeke D, Stewart JR, Sandler MP. Evaluation of pulmonary lesions with FDG-PET. Comparison of findings in patients with and without a history of prior malignancy. Chest 1996;109:982-8. |
|13.||Lowe VJ, Duhaylongsod FG, Patz EF, Delong DM, Hoffman JM, Wolfe WG, et al. Pulmonary abnormalities and PET data analysis: a retrospective study. Radiology 1997;202:435-9. |
|14.||Kubota K, Matsuzawa T, Fujiwara T, Ito M, Hatazawa J, Ishiwata K, et al. Differential diagnosis of lung tumor with positron emission tomography: a prospective study. J Nucl Med 1990;31: 1927-32. |
|15.||Coleman RE, Laymon CM, Turkington TG. FDG imaging of lung nodules: a phantom study comparing SPECT, camera-based PET, and dedicated PET. Radiology 1999;210:823-8. |
|16.||Shreve PD, Steventon RS, Deters EC, Kison PV, Gross MD, Wahl RL. Oncologic diagnosis with 2-[fluorine-18]fluoro-2-deoxy-D-glucose imaging: dual-head coincidence gamma camera versus positron emission tomographic scanner. Radiology 1998;207:431-7. |
|17.||Bury T, Dowlati A, Paulus P, Corhay JL, Benoit T, Kayembe JM, et al. Evaluation of the solitary pulmonary nodule by positron emission tomography imaging. Eur Respir J 1996;9:410-4. |
|18.||Gupta NC, Maloof J, Gunel E. Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 1996;37:943-8. |
|19.||Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 200121;285:914-24. |
|20.||Gambhir SS, Shepherd JE, Shah BD, Hart E, Hoh CK, Valk PE, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol 1998;16:2113-25. |
|21.||Kazerooni EA, Lim FT, Mikhail A, Martinez FJ. Risk of pneumothorax in CT-guided transthoracic needle aspiration biopsy of the lung. Radiology 1996;198:371-5. |
|22.||Quint LE, Francis IR. Radiologic staging of lung cancer. J Thorac Imaging. 1999;14:235-46. |
|23.||Bittner RC, Felix R. Magnetic resonance (MR) imaging of the chest: state-of-the-art. Eur Respir J 1998;11:1392-404. |
|24.||Webb WR, Golden JA. Imaging strategies in the staging of lung cancer. Clin Chest Med 1991;12:133-50. |
|25.||Steinert HC, Hauser M, Allemann F, Engel H, Berthold T, von Schulthess GK, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 1997;202:441-6. |
|26.||Pieterman RM, van Putten JW, Meuzelaar JJ, Mooyaart EL, Vaalburg W, Koeter GH, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343:254-61. |
|27.||Dwamena BA, Sonnad SS, Angobaldo JO, Wahl RL. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s-meta-analytic comparison of PET and CT. Radiology 1999;213:530-6. |
|28.||D'Amico TA, Wong TZ, Harpole DH, Brown SD, Coleman RE. Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies. Ann Thorac Surg. 2002;74:160-3. |
|29.||Giraud P, Grahek D, Montravers F, Carette MF, Deniaud-Alexandre E, Julia F, et al. CT and (18)F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers. Int J Radiat Oncol Biol Phys 2001;49:1249-57. |
|30.||Schirrmeister H, Guhlmann A, Elsner K, Kotzerke J, Glatting G, Rentschler M, et al. Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med 1999;40:1623-9. |
|31.||Hustinx R, Paulus P, Jacquet N, Jerusalem G, Bury T, Rigo P. Clinical evaluation of whole-body 18F-fluorodeoxyglucose positron emission tomography in the detection of liver metastases. Ann Oncol 1998;9:397-401. |
|32.||Pandit N, Gonen M, Krug L, Larson SM. Prognostic value of [18F]FDG-PET imaging in small cell lung cancer. Eur J Nucl Med Mol Imaging 2003;30:78-84. |
|33.||Hauber HP, Bohuslavizki KH, Lund CH, Fritscher-Ravens A, Meyer A, Pforte A. Positron emission tomography in the staging of small-cell lung cancer: a preliminary study. Chest 2001;119:950-4. |
|34.||Lamki LM. Positron emission tomography, bronchogenic carcinoma, and the adrenals. AJR Am J Roentgenol 1997;168:1361-2. |
|35.||Bury T, Corhay JL, Duysinx B, Daenen F, Ghaye B, Barthelemy N, et al. Value of FDG-PET in detecting residual or recurrent nonsmall cell lung cancer. Eur Respir J 1999;14:1376-80. |
|36.||Patz EF Jr, Goodman PC. Positron emission tomography imaging of the thorax. Radiol Clin North Am 1994;32:811-23. |
|37.||Patz EF Jr. 1999 plenary session: Friday imaging symposium: evaluation of focal pulmonary abnormalities with FDG PET. Radiographics 2000;20:1182-5. |
|38.||Frank A, Lefkowitz D, Jaeger S, Gobar L, Sunderland J, Gupta N, et al. Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings. Int J Radiat Oncol Biol Phys 1995;32:1495-512. |
|39.||Hebert ME, Lowe VJ, Hoffman JM, Patz EF, Anscher MS. Positron emission tomography in the pretreatment evaluation and follow-up of non-small cell lung cancer patients treated with radiotherapy: preliminary findings. Am J Clin Oncol 1996;19:416-21. |
|40.||Hicks RJ, Kalff V, MacManus MP, Ware RE, McKenzie AF, Matthews JP. The utility of (18)F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification. J Nucl Med 2001;42:1605-13. |
|41.||Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999;49:8-31. |
|42.||Wingo PA, Cardinez CJ, Landis SH, Greenlee RT, Ries LA, Anderson RN, et al. Long-term trends in cancer mortality in the United States, 1930-1998. Cancer 2003;97(12 Suppl):3133-275. |
|43.||Chu KC, Tarone RE, Chow WH, Hankey BF, Ries LA. Temporal patterns in colorectal cancer incidence, survival, and mortality from 1950 through 1990. J Natl Cancer Inst 1994;86:997-1006. |
|44.||Abdel-Nabi H, Doerr RJ, Lamonica DM, Cronin VR, Galantowicz PJ, Carbone GM, et al. Staging of primary colorectal carcinomas with fluorine-18 fluorodeoxyglucose whole-body PET: correlation with histopathologic and CT findings. Radiology 1998;206:755-60. |
|45.||Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H, et al. PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 1991;32:1485-90. |
|46.||Vitola JV, Delbeke D, Meranze SG, Mazer MJ, Pinson CW. Positron emission tomography with F-18-fluorodeoxyglucose to evaluate the results of hepatic chemoembolization. Cancer. 1996;78: 2216-22. |
|47.||Findlay M, Young H, Cunningham D, Iveson A, Cronin B, Hickish T, et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 1996;14:700-8. |
|48.||August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev 1984;3:303-24. |
|49.||Steele G Jr, Bleday R, Mayer RJ, Lindblad A, Petrelli N, Weaver D. A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584. J Clin Oncol 1991;9:1105-12. |
|50.||Valk PE, Abella-Columna E, Haseman MK, Pounds TR, Tesar RD, Myers RW, et al. Whole-body PET imaging with [18F] fluorodeoxyglucose in management of recurrent colorectal cancer. Arch Surg 1999;134:503-11. |
|51.||Delbeke D, Vitola JV, Sandler MP, Arildsen RC, Powers TA, Wright JK Jr, et al. Staging recurrent metastatic colorectal carcinoma with PET. J Nucl Med 1997;38:1196-201. |
|52.||Lai DT, Fulham M, Stephen MS, Chu KM, Solomon M, Thompson JF, et al. The role of whole-body positron emission tomography with [18F] fluorodeoxyglucose in identifying operable colorectal cancer metastases to the liver. Arch Surg 1996;131:703-7. |
|53.||Hickeson M, Yun M, Matthies A, Zhuang H, Adam LE, Lacorte L, et al. Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging. 2002;29:1639-47. |
|54.||Valk PE, Pounds TR, Hopkins DM, Haseman MK, Hofer GA, Greiss HB et al. Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995;60:1573-81. |
|55.||Wahl RL, Cody RL, Hutchins GD, Mudgett EE. Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1991;179:765-70. |
|56.||Bruce DM, Evans NTS, Heys SD, Needham G, Ben Younes H, Mikecz P, et al. Positron emission tomography: 2-deoxy-2-[18F]-fluoro-D-glucose uptake in locally advanced breast cancers. Eur J Surg Oncol 1995;21:280-3. |
|57.||Avril N, Dose J, Janicke F, Bense S, Ziegler S, Laubenbacher C, et al. Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose. J Clin Oncol 1996;14:1848-57. |
|58.||Avril N, Menzel M, Dose J, Schelling M, Weber W, Janicke F, et al. Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med 2001;42:9-16. |
|59.||Schirrmeister H, Kuhn T, Guhlmann A, Santjohanser C, Horster T, Nussle K, et al. Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures. Eur J Nucl Med 2001;28:351-8. |
|60.||Buck A, Schirrmeister H, Kuhn T, Shen C, Kalker T, Kotzerke J, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging 2002;29:1317-23. |
|61.||Crippa F, Agresti R, Seregni E, et al. Prospective evaluation of fluorine-18-FDG PET in presurgical staging of axilla in breast cancer. J Nucl Med 1998;39:4-9. |
|62.||Uteh CI, Young CS, Winter PF. Prospective evaluation of F-18FDG positron emission tomography in breast cancer for staging of axilla related to surgery and immunocytochemistry. Eur J Nucl Med 1996;23:1588-92. |
|63.||Yutani K, Tatsumi M, Shiba E, Kusuoka H, Nishimura T. Comparison of dual-head coincidence gamma camera FDG imaging with FDG PET in detection of breast cancer and axillary lymph node metastasis. J Nucl Med 1999;40:1003-8. |
|64.||Kumar R, Jana S, Heiba SI, Dakhel M, Axelrod D, Siegel B, et al. Retrospective analysis of sentinel node localization in multicentric palpable and non-palpable breast cancer. J Nucl Med 2003:44:7-10 |
|65.||Eltahir A, Heys SD, Hutcheon AW, Sarkar TK, Smith I, Walker LG, et al. Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg. 1998;175:127-32. |
|66.||Gazet JC, Coombes RC, Ford HT, Griffin M, Corbishley C, Makinde V, et al. Assessment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer. Br J Cancer. 1996;73:758-62. |
|67.||Bergh J, Jonsson PE, Glimelius B, Nygren P. A systematic overview of chemotherapy effects in breast cancer. Acta Oncol 2001;40:253-81. |
|68.||Wang H-C, Lo S-S. Future prospects of neoadjuvant chemotherapy in treatment of primary breast cancer. Semin Surg Oncol 1996;12:59-66. |
|69.||Wahl RL, Zasadny K, Helvie M, Hutchins GD, Weber B, Cody R. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography:initial evaluation. J Clin Oncol 1993;11:2101-11. |
|70.||Jansson T, Westlin JE, Ahlstrom H, Lilja A, Langstrom B, Bergh J. Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation? J Clin Oncol 1995;13:1470-7. |
|71.||Schelling M, Avril N, Nahrig J, Kuhn W, Romer W, Sattler D, et al. Positron emission tomography using [(18)F]fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 2000;18:1689-95. |
|72.||Bassa P, Kim EE, Inoue T, Wong FC, Korkmaz M, Yang DJ, et al. Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 1996;37:931-8. |
|73.||Smith IC, Welch AE, Hutcheon AW, Miller ID, Payne S, Chilcott F, et al. Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 2000;18:1676-88. |
|74.||Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ, et al. Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 2002;43:500-9. |
|75.||Vranjesevic D, Filmont JE, Meta J, Silverman DH, Phelps ME, Rao J, et al. Whole-body (18)F-FDG PET and conventional imaging for predicting outcome in previously treated breast cancer patients. J Nucl Med 2002;43:325-9. |
|76.||van Dongen JA, Voogd AC, Fentiman IS, Legrand C, Sylvester RJ, Tong D, et al. Long term results of a randmised trial comparing breast conserving therapy and mastectomy: Europian organization for research and treatment of cancer 10801 trial. J Natl Cancer Inst 2000;92:1143-50. |
|77.||Probstfeld MR, O'Connell TX. Treatment of locally breast carcinoma. Arch Surg 1989;124:1127-9. |
|78.||Schwaibold F, Fowble BL, Solin LJ, Schultz DJ, Goodman RL. The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys 1991;21:299-310. |
|79.||Whal RL. Current status of breast cancer imaging, staging and therapy. Semin Roentgenol 2001;36:250-60. |
|80.||Gallowitsch HJ, Kresnik E, Gasser J, Kumnig G, Igerc I, Mikosch P, et al. F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging. Invest Radiol. 2003;38:250-6. |
|81.||Kamel EM, Wyss MT, Fehr MK, von Schulthess GK, Goerres GW. [18F]-Fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer. J Cancer Res Clin Oncol 2003;129:147-53. |
|82.||Eubank WB, Mankoff DA, Vesselle HJ, Eary JF, Schubert EK, Dunnwald LK, et al. Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET. Radiographics 2002;22:5-17. |
|83.||Eubank WB, Mankoff DA, Takasugi J, Vesselle H, Eary JF, Shanley TJ, et al. 18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer. J Clin Oncol 2001;19:3516-23. |
|84.||Kao CH, Hsieh JF, Tsai SC, Ho YJ, Yen RF. Comparison and discrepancy of 18F-2-deoxyglucose positron emission tomography and tc-99m MDP bone scan to detect bone metastases. Anticancer Res 2000;20:2189-92. |
|85.||Sasaki M, Kuwabara Y, Koga H, Nakagawa M, Chen T, Kaneko K, et al. Clinical impact of wholebody FDG-PET on staging and therapeutic decision making for malignant lymphoma. Ann Nucl Med 2002;16:337-45. |
|86.||Einat Even-Sapir, Ora Israel. Gallium-67 scintigraphy: a cornerstone in functional imaging of lymphoma. Eur J Nucl Med and Mole Imag 2003;30:S65-S81. |
|87.||Moog F, Bangerter M, Diederichs CG, Guhlmann A, Kotzerke J, Merkle E, et al. Lymphoma: role of FDG-PET in nodal staging. Radiology 1997;203:795-800. |
|88.||Stumpe KD, Urbinelli M, Steinert HC, Glanzmann C, Buck A, von Sculthess GK. Whole body positron emission tomography using FDG for staging lymphoma: effectiveness and comparison with computed tomography. Eur J Nucl Med 1998;25:721-8. |
|89.||Cremerius U, Fabry U, Neuerburg J, Zimny M, Osieka R, Buell U. Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma. Nucl Med Commun. 1998;19:1055-63. |
|90.||Zinzani PL, Magagnoli M, Chierichetti F, Zompatori M, Garraffa G, Bendandi M, et al. The role of positron emission tomography (PET) in the management of lymphoma patients. Ann Oncol 1999;10:1181-4. |
|91.||Partridge S, Timothy A, O'Doherty MJ, Hain SF, Rankin S, Mikhaeel G. 2-Fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography in the pretreatment staging of Hodgkin's disease: influence on patient management in a single institute. Ann Oncol 2000;11:1273-9. |
|92.||Schoder H, Meta J, Yap C, Ariannejad M, Rao J, Phelps ME, et al. effect of whole body (18)F-FDG PET imaging on clinical staging and management of patients with malignant lymphoma. J Nucl Med 2001;42:1139-43. |
|93.||Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med 2000;27:1564-78. |
|94.||Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, et al. Whole body emission tomography using F-18- fluorodeoxyglucose for post treatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has a higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999;94:429-33. |
|95.||Mikhaeel NG, Timothy AR, Odoherty MJ, Hain S, Maisey MN. 18-FDG-PET as a prognostic indicator in the treatment of aggressive non-Hodgkin's lymphoma, comparison with CT. Leuk Lymphoma 2000;39:543-53. |
|96.||Juweid ME, Wiseman GA, Menda Y, Vose J, Links B, Graham MM. FDG-PET in the prediction of progression free survival at 1-year of patients with aggressive non-Hodgkin's lymphoma following antracycline based first line chemotherapy. Eur J Nucl Med 2002;29:S264. |
|97.||Spaepen K, Stroobants S, Dupont P, et al. Can positron emission tomography using 18-F- fluorodeoxy glucose ((18)F-FDG PET) after first line treatment distinguish Hodgkin's disease patients who need additional therapy from others where additional therapy would mean avoidable toxicity? Br J Haematol 2001;115:272-8. |
|98.||Mikhaeel NG, Mainwaring P, Nunan T, Timothy AR. Prognostic value of interim and post treatment FDG-PET scanning Hodgkin's lymphoma. Ann Oncol 2002;13:21-2. |
|99.||Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma ad Hodgkin's disease. J Nucl Med 2002;43:1018-27. |
|100.||Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol 1988;6:931-3. |
|101.||Lowe V, Wiseman GA. Assessment of lymphoma therapy using 18F-FDG-PET. J Nucl Med 2002;43:1028-30. |
|102.||Hoskin P, FDG PET in management of lymphoma: a clinical prespective. Eur J Nucl Med 2002;28:449-51. |
|103.||Front D, Bar-Shalom R, Mor M, Haim N, Epelbaum R, Frenkel A, et al. Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy. Radiology 2000;214:253-7. |
|104.||Cremerius U, Fabry U, Kroll U, Zimny M, Neuerburg J, Osieka R, et al. Clinical value of FDG PET for therapy monitoring of malignant lymphoma: results of a retrospective study in 72 patients. Nuklearmedizin 1999;38:24-30. |
|105.||Mikosch P, Gallowitsch HJ, Zinke-Cerwenka W, Heinisch M, Pipam W, Eibl M, et al. Accuracy of whole-body 18F-FDG-PET for restaging malignant lymphoma. Acta Medica Austriaca 2003;30:410-47. |
|106.||Hollenbeak CS, Lowe VJ, Stack BC. The cost-effectiveness of fluorodeoxyglucose 18-F positron emission tomography in the N0 neck. Cancer 2001;92:2341-8. |
|107.||Davis JP, Maisey NM, Chevreton EB. Positron emission tomography: a useful imaging technique for otolaryngology, head and neck surgery? J Laryngol Otol 1998;112:125-7. |
|108.||Adams S, Baum RP, Stuckensen T, Bitter K, Hor G. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25:1255-60. |
|109.||Kau RJ, Alexiou C, Laubenbacher C, Werner M, Schwaiger M, Arnold W. Lymph node detection of head and neck squamous cell carcinomas by positron emission tomography with fluorodeoxyglucose F 18 in a routine clinical setting. Arch Otolaryngol Head Neck Surg 1999;125:1322-8. |
|110.||McGuirt WF, Greven K, Williams D 3rd, Keyes JW Jr, Watson N, Cappellari JO, et al. PET scanning in head and neck oncology: a review. Head Neck 1998;20:208-15. |
|111.||Braams JW, Pruim J, Kole AC, Nikkels PG, Vaalburg W, Vermey A, et al. Detection of unknown primary head and neck tumors by positron emission tomography. Int J Oral Maxillofac Surg 1997;26:112-5. |
|112.||Fischbein NJ, AAssar OS, Caputo GR, Kaplan MJ, Singer MI, Price DC, et al. Clinical utility of positron emission tomography with 18F-fluorodeoxyglucose in detecting residual/recurrent squamous cell carcinoma of the head and neck. AJNR Am J Neuroradiol 1998;19:1189-96. |
|113.||Anzai Y, Carroll WR, Quint DJ, Bradford CR, Minoshima S, Wolf GT, et al. Recurrence of head and neck cancer after surgery or irradiation: prospective comparison of 2-deoxy-2-[F-18]fluoro-D-glucose PET and MR imaging diagnoses. Radiology 1996;200:135-41. |
|114.||Wong WL, Chevretton EB, McGurk M, Hussain K, Davis J, Beaney R, et al. A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma. Clin Otolaryngol 1997;22:209-14. |
|115.||McGuirt WF, Greven KM, Keyes JW Jr, Williams DW 3rd, Watson NE Jr, Geisinger KR, et al. Positron emission tomography in the evaluation of laryngeal carcinoma. Ann Otol Rhinol Laryngol 1995;104:274-8. |
|116.||Lowe VJ, Dunphy FR, Varvares M, Kim H, Wittry M, Dunphy CH, et al. Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography. Head Neck 1997;19:666-74. |
|117.||McGuirt WF, Keyes JW Jr, Greven KM, Williams DW 3rd, Watson NE Jr, Cappellari JO. Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography. Laryngoscope 1995;105:579-84. |
|118.||Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 2002;24:127-35. |
|119.||Damian DL, Fulham MJ, Thompson E, Thomason JF. Positron emission tomography in detection and management oh malignant malenoma. Malenoma Res 1996;6:325-9. |
|120.||Tyler DS, Onaitis M, Kherani A, Hata A, Nicholson E, Keogan M, et al. Positron emission tomography scanning in malignant melanoma: clinical utility in patients with stage III disease. Cancer 2000;89:1019-25. |
|121.||Wagner JD, Schauwecker D, Davidson D, Coleman JJ 3rd, Saxman S, Hutchins G, et al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol 1999;17:1508-15. |
|122.||Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma patients with whole-body 8F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 1998;82:1664-71. |
|123.||Holder WD Jr, White RL Jr, Zuger JH, Easton EJ Jr, Greene FL. Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 1998;227:764-9. |
|124.||Flanagan FL, Dehdashti F, Siegel BA, Trask DD, Sundaresan SR, Patterson GA, et al. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol 1997;168:417-24. |
|125.||Rankin SC, Taylor H, Cook GJ, Mason R. Computed tomography and positron emission tomography in the pre-operative staging of oesophageal carcinoma. Clin Radiol 1998;53:659-65. |
|126.||Skehan SJ, Brown AL, Thompson M, Young JE, Coates G, Nahmias C. Imaging features of primary and recurrent esophageal cancer at FDG PET. Radio Graphics 2000;20:713-23. |
|127.||Brucher BL, Weber W, Bauer M, Fink U, Avril N, Stein HJ, et al. Neoadjuvant therapy of esophageal squamous cell carcinoma: response to therapy evaluation by positron emission tomography. Ann Surg 2001;233:300-9. |
|128.||Kim K, Park SJ, Kim BT, Lee KS, Shim YM. Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography. Ann Thorac Surg 2001;71:290-4. |
|129.||Kelly S, Harris KM, Berry E, Hutton J, Roderick P, Cullingworth J, et al. A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma. Gut 2001;49:534-9. |
|130.||Jadvar H, Conti PS. Diagnostic utility of FDG PET in multiple myeloma. Skeletal Radiol 2002;31:690-4. |
|131.||El-Shirbiny AM, Yeung H, Imbriaco M, et al. Tc99m-MIBI versus fluorine-18-FDG in diffuse multiple myeloma. J Nucl Med 1997;38:1208-10. |
|132.||Schirrmeister H, Bommer M, Buck AK, Muller S, Messer P, Bunjes D, et al. Initial results in the assessment of multiple myeloma using 18F-FDG PET. Eur J Nucl Med 2002;29:361-6. |
|133.||Orchard K, Barrington S, Buscombe J, Hilson A, Prentice HG, Mehta A. Fluoro-deoxyglucose positron emission tomography imaging for the detection of occult disease in multiple meloma. Br J Haematol 2002;117:133-5. |
|134.||Eary JF, O'Sullivan F, Powitan Y, Chandhury KR, Vernon C, Bruckner JD, et al. Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis. Eur J Nucl Med 2002;29:1149-54. |
|135.||Eary JF, Conrad EU. Positron emission tomography in grading soft tissue sarcomas. Semin Musculoskelet Radiol 1999;3:135-8. |
|136.||Eary JF, Conrad EU, Bruckner JD, Folpe A, Hunt KJ, Mankoff DA, et al. Quantitative [F-18]fluorodeoxyglucose positron emission tomography in pretreatment and grading of sarcoma. Clin Cancer Res 1998;4:1215-20. |
|137.||Lucas JD, O'Doherty MJ, Wong JC, Bingham JB, McKee PH, Fletcher CD, et al. Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas. J Bone Joint Surg Br 1998;80:441-7. |
|138.||Brenner W, Bohuslavizki KH, Eary JF. PET imaging of osteosarcoma. J Nucl Med 2003;44:930-42. |
|139.||Scott AM. Current status of positron emission tomography in oncology. Australas Radiol 2002;46:154-62. |
|140.||Karlan BY, Hawkins R, Hoh C, Lee M, Tse N, Cane P, et al. Whole-body positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose can detect recurrent ovarian carcinoma. Gynecol Oncol 1993;51:175-81. |
|141.||Hubner KF, McDonald TW, Niethammer JG, Smith GT, Gould HR, Buonocore E. Assessment of primary and metastatic ovarian cancer by positron emission tomography (PET) using 2-[18F]deoxyglucose (2-[18F]FDG). Gynecol Oncol 1993;51:197-200. |
|142.||Greven KM, Keyes JW Jr, Williams DW 3rd, McGuirt WF, Joyce WT 3rd. Occult primary tumors of the head and neck: lack of benefit from positron emission tomography imaging with 2-[F-18] fluoro-2-deoxy-D-glucose. Cancer 1999;86:114-8. |
|143.||Lassen U, Daugaard G, Eigtved A, Damgaard K, Friberg L. 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT). Eur J Cancer 1999;35:1076-82. |
|144.||Bohuslavizki KH, Klutmann S, Kroger S, Sonnemann U, Buchert R, Werner JA, et al. FDG PET detection of unknown primary tumors. J Nucl Med 2000;41:816-22. |
|145.||Rades D, Kuhnel G, Wildfang I, Borner AR, Schmoll HJ, Knapp W. Localized disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management. Ann Oncol 2001;12:1605-9. |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10]
[Table - 1]
|This article has been cited by|
||Assessment of therapy response by FDG PET in infection and inflammation
| ||Kumar, R. and Karunanithi, S. and Zhuang, H. and Alavi, A. |
| ||PET Clinics. 2012; 7(2): 233-243 |
||The use and importance of liposomes in Positron Emission Tomography
| ||Silindir, M. and Ã–zer, A.Y. and ErdogÇŽan, S. |
| ||Drug Delivery. 2012; 19(1): 68-80 |
||Role of FDG PET-CT in recurrent renal cell carcinoma
| ||Kumar, R., Shandal, V., Shamim, S.A., Jeph, S., Singh, H., Malhotra, A. |
| ||Nuclear Medicine Communications. 2010; 31(10): 844-850 |
||Role of FDG-PET/CT in detection of recurrent disease in colorectal cancer
| ||Shamim, S.A., Kumar, R., Halanaik, D., Shandal, V., Reddy, R.M., Bal, C.S., Malhotra, A. |
| ||Nuclear Medicine Communications. 2010; 31(6): 590-596 |
||A case of pathologic fracture of femur whose primary tumor and occult metastases were ascertained by PET-CT
| ||Yoo, J.H., Yang, B.K., Kim, J.H., Kim, S., Kim, E.S. |
| ||Archives of Orthopaedic and Trauma Surgery. 2009; 129(2): 155-159 |
||Dual time point FDG-PET/CT imaging... Potential tool for diagnosis of breast cancer
| ||Zytoon, A.A., Murakami, K., El-Kholy, M.R., El-Shorbagy, E. |
| ||Clinical Radiology. 2008; 63(11): 1213-1227 |
||Impact of dual-time-point 18F-FDG PET imaging and partial volume correction in the assessment of solitary pulmonary nodules
| ||Alkhawaldeh, K., Bural, G., Kumar, R., Alavi, A. |
| ||European Journal of Nuclear Medicine and Molecular Imaging. 2008; 35(2): 246-252 |
||Primary ovarian lymphoma with central nervous system infiltration [Linfoma primario de ovario con afectaciÃ³n a sistema nervioso central]
| ||Rosas-Cabral, A. and Alatriste-MartÃnez, S. and MuÃ±oz-FernÃ¡ndez, L. and Bernal-LÃ³pez, C. and DÃ¡vila-de la Llave, G. and Vela-Rivera, C. |
| ||Cirugia y Cirujanos. 2008; 76(6): 523-528 |
||Squamous cell carcinoma of the scalp arising from chronic discoid lupus erythematosus with scarring alopecia
| ||Hu, S.C.-S., Chen, Y.-W., Chen, G.-S., Cheng, S.-T. |
| ||Dermatologica Sinica. 2007; 25(2): 165-170 |
||Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging
| ||Zavaleta, C.L., Phillips, W.T., Bradley, Y.C., McManus, L.M., Jerabek, P.A., Goins, B.A. |
| ||International Journal of Gynecological Cancer. 2007; 17(2): 407-417 |
||Value of PET restaging after chemotherapy for non-Hodgkinæs lymphoma: Implications for consolidation radiotherapy
| ||Kahn, S.T., Flowers, C., Lechowicz, M.J., Hollenbach, K., Johnstone, P.A.S. |
| ||International Journal of Radiation Oncology Biology Physics. 2006; 66(4): 961-965 |
||Increased FDG uptake in pulmonary epitheloid hemangioendothelioma
| ||Ergün, E.L., Lim, E. |
| ||Revista Espanola de Medicina Nuclear. 2006; 25(3): 188-192 |
||Synthesis and evaluation of a technetium-99m-labeled diethylenetriaminepentaacetate-deoxyglucose complex ([99mTc]-DTPA-DG) as a potential imaging modality for tumors
| ||Chen, Y., Wen Huang, Z., He, L., Long Zheng, S., Lian Li, J., Lian Qin, D. |
| ||Applied Radiation and Isotopes. 2006; 64(3): 342-347 |
||Assessment of Therapy Response by Fluorine-18 Fluorodeoxyglucose PET in Infection and Inflammation
| ||Kumar, R., Chauhan, A., Zhuang, H., Alavi, A. |
| ||PET Clinics. 2006; 1(2): 191-198 |
||18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: Comparison with long-term clinical outcome
| ||Tran, A., Pio, B.S., Khatibi, B., Czernin, J., Phelps, M.E., Silverman, D.H.S. |
| ||Journal of Nuclear Medicine. 2005; 46(9): 1455-1459 |
||Molecular nuclear imaging: The radiopharmaceuticals (review)
| ||Imam, S.K. |
| ||Cancer Biotherapy and Radiopharmaceuticals. 2005; 20(2): 163-172 |
||FDG-PET imaging in primary bilateral adrenal lymphoma: A case report and review of the literature
| ||Kumar, R., Xiu, Y., Mavi, A., El-Haddad, G., Zhuang, H., Alavi, A. |
| ||Clinical Nuclear Medicine. 2005; 30(4): 222-230 |
||Reflux esophagitis secondary to chemotherapy detected by serial FDG-PET
| ||Bural, G.G., Kumar, R., Mavi, A., Alavi, A. |
| ||Clinical Nuclear Medicine. 2005; 30(3): 182-183 |
||Potential of dual-time-point imaging to improve breast cancer diagnosis with 18F-FDG PET
| ||Kumar, R., Loving, V.A., Chauhan, A., Zhuang, H., Mitchell, S., Alavi, A. |
| ||Journal of Nuclear Medicine. 2005; 46(11): 1819-1824 |
||PET in the management of urologic malignancies
| ||Kumar, R., Zhuang, H., Alavi, A. |
| ||Radiologic Clinics of North America. 2004; 42(6): 1141-1153 |
||Utility of fluorodeoxyglucose-PET imaging in the management of patients with Hodgkinæs and non-Hodgkinæs lymphomas
| ||Kumar, R., Maillard, I., Schuster, S.J., Alavi, A. |
| ||Radiologic Clinics of North America. 2004; 42(6): 1083-1100 |
||Positron emission tomography: An advanced nuclear medicine imaging technique from research to clinical practice
| ||Kumar, R., Jana, S. |
| ||Methods in Enzymology. 2004; 385: 3-19 |