| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
aVanderbilt University Medical Center, Nashville, Tennessee, USA; bUniversity Hospital, Gasthuisberg, Leuven, Belgium; cHôpital Saint-Louis, Paris, France; dHôpital Henri Mondor, Creteil, France; eUniversity of Southern California, Los Angeles, California, USA
Key Words. Positron emission tomography • Emission-computed tomography • Non-Hodgkin's lymphoma • Imaging
Correspondence: Peter S. Conti, M.D., Ph.D., Department of Radiology, University of Southern California, 1510 San Pablo Street, Room #350, Los Angeles, California 90033, USA. Telephone: 323-442-5940; Fax: 323-442-5778; e-mail: pconti{at}usc.edu
Received March 27, 2009; accepted for publication July 14, 2009.
Disclosures: Dominique Delbeke: Honoraria: GE Healthcare; Sigrid Stroobants: None; Eric de Kerviler: None; Christian Gisselbrecht: Research funding/contracted research: Bayer Schering Pharma; Michel Meignan: None: Peter S. Conti: Honoraria: Bayer Schering.
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.
 |
ABSTRACT |
|---|
 Top Abstract IntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
|
INTRODUCTION |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
Staging of malignant lymphoma is usually performed using computed tomography (CT) [1]. However, the lack of functional information from CT can impede the identification of disease in normal-sized tissue [4]. An alternative to CT is 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), which is based on the increased glycolysis of cancer cells. This is visualized using the radioactive glucose analog FDG, which after phosphorylation is metabolically trapped within the cell [5]. Thus, in addition to CT, FDG-PET has become an established imaging modality to stage, restage, monitor therapy, and detect recurrent lymphoma. PET (metabolic information) and CT (anatomical information) are complementary, and interpretation of the PET portion of the study is more accurate when PET is correlated with CT [4, 6, 7]. Therefore, by 2000, integrated PET/CT systems were developed that are now the standard of care. Figure 1 demonstrates a typical PET/CT image that can be obtained using these devices. In the U.S., 
90% of the PET systems currently in operation are integrated PET/CT systems [8].
|
|
CHESON CRITERIA TO DEFINE TREATMENT RESPONSE IN LYMPHOMA |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
One of the main criticisms of the 1999 guidelines related to the interpretation of an unconfirmed complete response (CRu) and one of the advantages of PET is that it can distinguish between viable tumor and necrosis or fibrosis in residual masses [10, 12]. Indeed, a retrospective study carried out by Juweid et al. [13] in 2005 demonstrated that integration of PET into the IWG criteria increased the number of confirmed complete responses (CRs), eliminating the need for the CRu category. Thus, the revised criteria state that, in routinely FDG-avid lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and HL, a CR is assigned to all patients with a negative PET scan regardless of the presence of a residual mass on CT. In cases in which there is residual disease on PET (PET-positive patients), a partial response, stable disease, or progressive disease can be assigned based on the response shown by CT; the CRu category is eliminated (Table 1) [10].
|
|
DEGREE OF FDG AVIDITY OF DIFFERENT TYPES OF LYMPHOMA |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
85% of lymphomas [15]. NHL can also be divided into two prognostic groups: the indolent lymphomas and the aggressive lymphomas. Patients with indolent NHL subtypes have a relatively good prognosis, with a median survival duration as long as 10 years, but they are not usually curable in advanced clinical stages. DLBCL is the most common aggressive lymphoma, representing 30% of NHL cases; other relatively common aggressive lymphomas include mantle cell lymphoma (MCL) and adult T-cell leukemia/lymphoma, representing 6% and 8% of NHL cases, respectively [15]. Follicular lymphoma (FL) is the most common type of indolent lymphoma, representing 22% of NHL cases [15]; marginal zone lymphoma (MZL) and small-cell lymphocytic lymphoma (SLL) are other types of indolent lymphoma, representing 6% and 8% of NHL cases, respectively [15]. The degree of FDG uptake can be evaluated semiquantitatively using the standardized uptake value (SUV). The SUV is the activity in the lesion in µCi/ml corrected for the weight of the patient and the dose of FDG administered, and the use of SUVs is further addressed in a later section in this manuscript. Although there is an overlap in SUV between aggressive and indolent NHL, the SUV in aggressive NHL and HL is generally significantly higher than SUVs obtained for indolent lymphomas [16]; for example, HL and aggressive NHL types such as DLBCL and grade III FL have a high uptake of FDG (mean SUVs in newly diagnosed patients of 17.1 and 16.0, respectively), whereas FDG uptake in MCL, MZL, and grade I–II FL is clearly lower (mean SUVs in newly diagnosed patients of 6.0, 9.5, and 7.0, respectively) [16] (Table 2).
|
Image-Guided Needle Biopsies
Image-guided needle biopsies (IGNBs) are particularly useful for the diagnosis of new patients, or patients who require restaging as a result of incomplete subtyping or progression. A needle is inserted into the abnormal region, guided by imaging techniques, and a tissue biopsy is taken for histological diagnosis. It is advantageous because it can be used with all patients of any age (including children) and all targets that are reachable (including deep lymph nodes). IGNBs can be performed on an outpatient basis under local anesthesia and allow rapid diagnosis and therapy choices to be made [22, 23]. IGNBs are not limited to CT, because PET can also be used to guide biopsies to the site of highest FDG uptake, representing the most aggressive site of lymphoma [21]. The overall diagnostic yield of IGNBs in patients with lymphoma is in the range of 90%–96% [22, 23].
|
GUIDELINES FOR USING FDG-PET AND CT OR PET/CT IMAGING IN LYMPHOMA |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
The guidelines regarding the use of PET/low-dose CT are based on several studies that concluded that PET/low-dose CT may be adequate for most patients and that CECT may be recommended for selected cases. For example, there is evidence to suggest that PET/CT performed without CECT is sufficient to detect peripheral lymph nodes or other extranodal lesions that may not be detected by PET [24–27]. PET/low-dose CT and PET/CECT were compared in 47 patients with lymphoma. On a region-based analysis, there was no significant difference for the detection of lymphoma. PET/CECT provided slightly fewer equivocal sites (two of 188) and allowed detection of slightly more extranodal sites (n = 4 of 188). For the purpose of staging, there was almost perfect agreement (46 of 47 patients) [28].
However, there are ongoing debates regarding when CECT should be used for the staging of lymphoma, because the number of lymphoma patients for whom potential benefits have been evaluated systematically is still too low to come to a definitive conclusion [29].
In addition, the National Comprehensive Cancer Network has incorporated FDG-PET in the evaluation and management algorithm of most HL and NHL patients [30]. The use of FDG-PET (PET/CT where available) is recommended in the following clinical scenarios: as a baseline for lymphomas that are potentially curative (HL, DLBCL), as a baseline to exclude systemic disease in clinically localized lymphoma (HL, DLBCL, FL, MCL, AIDS-related B-cell lymphoma, nodal and splenic MZL, peripheral T-cell lymphoma, mucosa-associated lymphoid tumors), to evaluate residual masses, and to monitor therapy of aggressive lymphoma (HL, DLBCL). FDG-PET is not indicated for monitoring therapy if the CT scan is normal, or for surveillance.
Guidelines for the Timing of FDG-PET Imaging After Therapy
A proposed schedule for the timing of PET scans is shown in Figure 2A and is based on the recommendations from Juweid et al. [11]. The timing of FDG-PET is critical to avoid equivocal interpretations. FDG-PET should be performed at least 3 weeks (preferably 6–8 weeks) after completion of chemotherapy and 8–12 weeks after radiation therapy because of radiation-induced inflammatory changes that can be FDG avid [31, 32]. It is also generally accepted that FDG-PET scans should be performed 2 months postsurgery. For evaluation during therapy, FDG-PET imaging should be performed as close as possible before the subsequent cycle of therapy.
|
Most lymphoma patients will become PET negative after two to three cycles of standard chemotherapy, and response assessments based on the new Cheson criteria are proving to be robust and highly predictive of outcome [35–37]. However, false-positive lesions occur more frequently at earlier time points, particularly with intensified schedules, and preliminary results indicate that the accuracy of PET differs depending on the given treatment [38]. In addition, with the increased use of more targeted therapies (such as immunotherapy, cell cycle inhibitors, and mammalian target of rapamycin inhibitors) whose antitumor activity is more gradual than classic cytotoxic therapies, the optimal timing and interpretation have yet to be identified [39]. A recent, small retrospective study indicated that, after treatment with either yttrium-90 (90Y)-ibritumomab tiuxetan (Zevalin®; Spectrum Pharmaceuticals, Inc., Irvine, CA; Bayer Schering Pharma AG, Berlin, Germany) or iodine-131 (131I)-tositumomab (Bexxar®; GlaxoSmithKline, Research Triangle Park, NC), response assessment should be delayed, although the authors noted that patients with the largest decrease in FDG uptake had a longer overall survival time [40].
Guidelines for the Timing of CT Post-therapy
The grade of lymphoma determines the timing of when CT is performed (Fig. 2B). Aggressive lymphomas, such as Burkitt's lymphoma or lymphoblastic lymphoma, are usually re-evaluated after one or two cycles of chemotherapy. In the case of HL and DLBCL, where recurrence is rare after 5 years, CT should be performed early (at four cycles) and frequently after treatment (for HL, this includes assessments every 6 months for 1–2 years after a CR and then every year for the next 3–5 years in favorable groups, more frequently in disseminated forms; for DLBCL,, assessment should occur every 6 months for 2 years and every year for 3 years, because recurrences are rare beyond this time scale). For patients with indolent NHL or FL who have experienced a CR, follow-up should be performed every 6 months for 1 year then every 6–12 months, because these patients are at continuous risk for relapse [11]). For patients with FL or low-grade lymphoma who are being monitored on a "watch and wait" basis, the frequency of follow-up should be specified in the protocol, because no consensus has been reached for this group [11]. Some teams also recommend clinical and biologic follow-up with a survey using ultrasound. This would be sufficient to document any bulky disease that may necessitate therapy.
|
PROCEDURE GUIDELINES FOR PERFORMING AND REPORTING PET AND PET/CT |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
PET Protocol
The National Cancer Institute has published similar recommendations [43] regarding patient preparation, uptake time, FDG dose, parameters for acquisition of images, and image analysis. For example, a patient must fast for 
4 hours prior to FDG administration and have a blood glucose level <200 mg/ml. FDG should be administered at a dose of 370–740 MBq and the distribution time should be 60 ± 10 minutes. The imaging time should be performed in accordance with the manufacturer's guidelines and attenuation correction should be performed.
CT Protocol: How Much CT Should Be Used?
The recently published revised Response Evaluation Criteria in Solid Tumors (RECIST) include recommendations for the optimal anatomical assessment of lesions, with new recommendations for lymph node imaging and clarification on the definition of disease progression [44]. A diagnostic CT (whether performed alone or as part of PET/CT) should be acquired following the standard guidelines: contiguous 
5-mm slices, from the lung apices to the symphysis pubis with i.v. and oral contrast obtained during a single breathhold [44]). CECT should be used for anatomically based RECIST measurements, although the CT portion of PET/CT can be used if it is of identical diagnostic quality to a diagnostic CT [44].
The rationale for not using CECT with all PET/CT studies is to minimize radiation to the patient in accordance with the "as low as reasonably achievable" principle. CT uses larger radiation doses than more common conventional x-ray imaging procedures, and the dose is dependent on a number of factors, including x-ray beam energy, tube current, rotation or exposure time, section and object thickness, and dose-reduction techniques [45]. The typical radiation dose of a chest/abdomen/pelvis CT using an optimized protocol for diagnostic CT is in the 25-mSv range, compared with an 8-mSv range for a low-dose CT with 80 mAs.
At these doses, the most likely risk is for radiation-induced carcinogenesis, although no large-scale epidemiologic studies of these risks have been reported [46]. Most risk assessments are based on extrapolation of the data collected from atomic bomb survivors. Although there is no consensus regarding the validity of extrapolation, these data suggest a statistically significant increase in the risk for cancer at radiation doses similar to those received by patients undergoing CT [47]. It has been estimated, using data from 1991–1996 on CT usage, that 0.4% of all cancers in the U.S. may be attributable to the radiation from CT [48]. Guidelines to optimize the protection of patients during CT procedures have been provided by various international organizations. These guidelines are described as diagnostic reference levels and are based on the weighted CT dose index and the distance length product that are now displayed on the console of every CT scanner [49].
Because most systems in operation are PET/CT systems, CT can be used at the very least to perform attenuation correction of the PET images. Such attenuation correction can be performed using low-dose CT (<30 mAs). A growing body of evidence has demonstrated that fusion PET/CT images provided by integrated PET/CT systems can improve lesion detection, lesion characterization as benign or malignant, and lesion localization [6, 7, 11], such that the CT portion of the study is now commonly performed without i.v. contrast and with a low-dose CT component (40–80 mAs) to reduce the radiation dose to the patient. However, the CT component can be performed using a diagnostic CT protocol with oral contrast and CECT as part of the PET/CT protocol rather than being performed separately. Recommendations regarding the necessity of CECT in the guidelines were addressed in an earlier section of this manuscript.
|
GUIDELINES FOR PET INTERPRETATION FOR RESPONSE ASSESSMENT IN LYMPHOMA |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
Recommendation on Visual Assessment Versus SUV
Consensus recommendations for the interpretation of FDG-PET for response assessment have been published by the imaging subcommittee of the International Harmonization Project. After completion of therapy, visual assessment alone is adequate for interpreting PET findings as positive or negative [11]. Mediastinal blood pool activity is used as a reference for the assessment of residual masses >2 cm. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow have been recommended.
Any diffuse or focal uptake in a location that is incompatible with normal anatomy/physiology should be considered as PET positive. The exception to this occurs when the residual mass is >2 cm in diameter and FDG uptake is lower than or equal to mediastinal blood pool structures; in these cases the PET status should be considered as negative [11].
If residual lesions are found in the spleen, liver, or bone marrow, other considerations need to be taken into account. Hepatic or splenic lesions >1.5 cm on CT should be considered as positive for lymphoma if their uptake is higher than or equal to that of the liver or spleen, and negative if their uptake is lower than that of the liver and spleen. If the lesion is <1.5 cm in diameter, the patient is considered as PET positive only if FDG uptake is greater than that of the liver or spleen.
Lung nodules 1.5 cm in patients should be considered as positive for lymphoma if FDG uptake is greater than the mediastinal blood pool. Lymphoma cannot be excluded in lung nodules <1.5 cm. New nodules in patients without established pulmonary lymphoma at baseline and who have evidence of a CR should be considered as negative for lymphoma, regardless of size and uptake, because they typically represent inflammatory lesions.
If there is a clearly multifocal increase in FDG uptake in the bone marrow, the patient can be considered as PET positive. The diffuse pattern of uptake of reactive bone marrow hyperplasia after chemotherapy, and especially after concurrent administration of bone marrow stimulants, can mimic or mask diffuse bone marrow involvement; therefore, appropriate history is critical. A delay of 3–4 weeks after completion of therapy permits the physiologic marrow activity to abate. Therefore, diffusely increased bone marrow uptake should not be misinterpreted as diffuse lymphomatous marrow involvement. A meta-analysis of PET for the evaluation of bone marrow infiltration demonstrated that PET had a good but not excellent correlation with bone marrow biopsies for the staging of HL and NHL [51]. The authors concluded that PET may complement the results of bone marrow biopsies and the diagnostic performance of PET may vary depending on the type of lymphoma; a more accurate result is obtained with HL and aggressive NHL than with indolent NHL [50]. Thus, a negative PET scan in the bone marrow does not exclude mild or moderate bone marrow involvement and bone marrow biopsy remains the standard of care.
Semiquantitative Analysis of PET Using SUV
The role of semiquantitative analysis of PET has not been fully determined. The SUV is the activity in the lesion in µCi/ml corrected for the weight of the patient and the dose of FDG administered. The SUV may be more accurate when measured relative to body surface area or lean body mass than to body weight. The average SUV of the normal liver parenchyma and blood pool is 2.0 and can be used as a visual reference. The SUV depends on accurate calibration of the PET system, accurate soft tissue attenuation correction, and reconstruction algorithms, among other factors. As CT transmission maps are acquired just before the acquisition of the emission data, attenuation correction can be compromised by imperfect registration of the transmission and emission images resulting from patient motion.
The SUV is also dependent on factors that are difficult to control in the clinical environment, such as the patient's plasma glucose and insulin levels, fasting state, dose infiltration, recent physical activity, and uptake time of FDG. In addition, there is inter- and intraobserver variability in identification of the lesion and slice with highest uptake and in drawing contours around the regions of interest. Thus, for the assessment of responses in a patient population, a comparison of SUVs between two studies requires rigorous quality control, especially if performed on different PET systems or using different protocols, and because of variation among institutions.
Therefore, current guidelines suggest that a visual assessment of PET status is adequate and sufficient for a positive or negative decision after completion of therapy; however, during treatment or in clinical trials, some form of semiquantitation may be helpful [11, 43, 52]. Cut-off levels of SUV to determine response to therapy are also likely to be dependent on tumor and treatment type and so need to be evaluated in further clinical trials.
Recommendations for Avoiding False Positives/Negatives
A list of etiologies for false-positive and false-negative interpretations is provided in both the SNM and the ACR guidelines for PET/CT in oncology [41, 42]; for example, physiologic uptake in response to therapy can occasionally confuse interpretation. Reactive diffuse bone marrow hyperplasia and splenic uptake occur typically for 2–4 weeks after chemotherapy and can be intense after administration of marrow-stimulating factors such as filgrastim. Thymic hyperplasia is common in children and young adults, with an incidence of 16%. It typically occurs 2–6 months after completion of therapy and may persist for 12–24 months. The pattern of moderate FDG uptake and the inverted V-shape are typical for thymic hyperplasia. FDG-avid inflammatory changes are usually seen matching radiation ports, for example, in radiation pneumonitis.
False-positive/negative interpretations can be avoided if FDG-PET is performed with appropriate patient preparation and interpreted with the knowledge of the type of lymphoma, clinical history, history of treatment, and correlative imaging studies. Therefore, published societal guidelines suggest that PET/CT should be interpreted by board-certified nuclear physicians or radiologists with the additional training and expertise in PET/CT recommended by professional societies, to minimize the occurrence of these false-positive/negative interpretations [41]. Alternatively, a central PET review network, such as the multisite online PET interpretations (IMOTEP) network in France, could be used to standardize interpretation.
Central Review of Groupe d'Etude des Lymphomes de l'Adulte (GELA) Within the Intergroup European Organization for Research and Treatment of Cancer/GELA-ILL H10 Protocol
IMOTEP was developed to use a reading procedure that can include the opinions of various experts in order to evaluate the results of early PET in clinical trials. This was deemed necessary because there are no consensus criteria for interpreting early PET scans [53]. The cornerstone of this network is the positoscope workstation, which allows side-by-side display of pre- and post-treatment PET/CT as well as complete image processing. The workstation can be used to send these files to the workstations of six experts located in France and Belgium, who can evaluate the scans independently and send their results to a centralized server where the results are integrated. The final results are then sent to the coordinating center and verified by the coordinating nuclear medicine physicist before being sent back to the investigator. All communication is carried out by mail and short message service, and the whole procedure can be carried out in <72 hours. The IMOTEP system was used extensively for the H10 protocol to standardize the early PET readings during that trial.
The H10 protocol is investigating the use of PET scans after two cycles of ABVD to modulate treatment strategies for patients with stage I/II HL [54]. Patients were initially randomized to the standard or investigational arm. In the standard arm, patients receive three cycles of ABVD plus involved-field radiotherapy in the favorable group or four cycles of ABVD plus radiotherapy in the unfavorable group, regardless of the PET result after two cycles. Patients in the experimental arm receive two cycles of ABVD followed by a PET scan to decide on a further treatment strategy. Patients who are PET negative continue with either two or four further cycles of ABVD without radiotherapy for favorable and unfavorable patients, respectively. Patients who are PET positive are switched to a salvage therapy with two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus involved-field radiotherapy. This study is ongoing and has recruited almost 800 patients as of January 2009.
All PET scans of the GELA group were interpreted using the IMOTEP network and the Juweid and Cheson published criteria. During an interim analysis of 148 patient scans that were submitted to the IMOTEP network, 10% of the final interpretations differed from the investigating center and 85% of these were changed from negative to positive results.
This trial and others have demonstrated the distinct advantages of central review: similar PET processing and analysis independent of which PET device is used, independent and online reading by any number of experts including those at the investigating center, fast transfer of PET images, compatibility with routine practice, security, and a fast turnaround for final results.
|
CONCLUSIONS |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
|
AUTHOR CONTRIBUTIONS |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
Provision of study materials or patients: Eric de Kerviler, Christian Gisselbrecht
Collection/assembly of data: Eric de Kerviler, Michel Meignan, Peter S. Conti
Data analysis and interpretation: Christian Gisselbrecht, Peter S. Conti
Manuscript writing: Dominique Delbeke, Sigrid Stroobants, Michel Meignan, Peter S. Conti
Final approval of manuscript: Dominique Delbeke, Sigrid Stroobants, Michel Meignan, Peter S. Conti
The authors take full responsibility for the scope, direction, and content of the manuscript and have approved the submitted manuscript. They would like to thank Lynda Chang, Ph.D., at Complete HealthVizion for her assistance in the preparation and revision of the draft manuscript, based on detailed discussion and feedback from all the authors. Editorial assistance was supported by a grant from Bayer HealthCare Pharmaceuticals.
|
ACKNOWLEDGMENTS |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
|
REFERENCES |
|---|
|
TopAbstractIntroductionCheson Criteria to Define...Degree of FDG Avidity...Guidelines for Using FDG-PET...Procedure Guidelines for...Guidelines for PET...ConclusionsAuthor ContributionsReferences |
|---|
t P et al. FDG-PET/CT in re-staging of patients with lymphoma. Eur J Nucl Med Mol Imaging 2004;31:325–329.[CrossRef][Medline]This article has been cited by other articles:
 |
|
 |
|
  A. Bischof Delaloye, P. S. Conti, C. Gisselbrecht, and S. A. Gregory Introduction Oncologist, October 1, 2009; 14(suppl_2): 1 - 3. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| THE ONCOLOGIST | STEM CELLS | CME | ALPHAMED PRESS JOURNALS |
