Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?

M. J. Reinhardt1,2,*, C. Herkel2, C. Altehoefer3, J. Finke4 and E. Moser2

1 Department of Nuclear Medicine, University Hospital Bonn, Bonn 2 Department of Nuclear Medicine, University Hospital Freiburg, Freiburg 3 Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg 4 Department of Hematology & Oncology, University Hospital Freiburg, Freiburg, Germany

* Correspondence to: Dr M. J. Reinhardt, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Tel: +49-228-287-5186; Fax: +49-228-287-1016; Email: michael.reinhardt{at}ukb.uni-bonn.de


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background: The aim of this study was to evaluate the accuracy of computed tomography (CT) and [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients after completion of therapy.

Patients and methods: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44 aggressive NHL patients (29 women, 72 men; aged 41±14 years) in a median of 2 months after therapy. Progression-free survival was evaluated using the Kaplan–Meier method. Independent prognostic factors were identified by means of Cox proportional hazards model.

Results: CT imaging results were progressive disease (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24 patients. Three-year progression-free survival rates after exclusion of five PD patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21% (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and bulky disease (P <0.05) were identified as independent prognostic variables.

Conclusions: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated those destined to progress into a low risk of ≤20% and a high risk for recurrence of ≥80%.

Key words: computed tomography, fluorodeoxyglucose, Hodgkin's disease, non-Hodgkin's lymphoma, positron emission tomography


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The response of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) to treatment has usually been documented using morphological cross-sectional imaging methods [1Go]. Computed tomography (CT) scans are frequently performed to detect asymptomatic relapse, but the accuracy of these studies has been compromised by their failure to detect small metastases and to differentiate residual masses consisting of fibrosis from those containing viable tumor cells [2Go, 3Go]. Approximately two-thirds of HD and half of NHL patients present with residual masses after completion of therapy, but only 20–25% will finally relapse [4Go, 5Go]. If the tumor is superficially localized it can easily be excised and histologically analyzed, but other localizations may be accessed only with a certain risk, owing to the necessity of anesthesia and surgery and a high failure rate considering the relatively small amount of tissue that can be gained by surgical or needle biopsies. Considering the large variety in time between completion of treatment and relapse, it would be desirable to identify patients who are at risk of relapse at a time when the tumor burden is small and to avoid additional unnecessary therapy in patients who are potentially cured. Therefore, identification of patients who are destined to progress remains a difficult but important task.

The effectiveness of [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for monitoring response to treatment in lymphoma patients has been shown in several studies during recent years [6Go]. Whether the oncologist might find combined analysis of post-therapeutic CT and FDG-PET advantageous for prediction of relapse in lymphoma patients is still unclear.

The objective of this study was to assess the accuracy of combined interpretation of morphological and functional cross-sectional imaging for prediction of individual response to treatment in HD and NHL patients.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients and treatment
Between June 1995 and May 2000, 101 consecutive patients with HD and NHL who received post-treatment FDG-PET and CT were entered into this retrospective analysis. These were 84 patients after primary therapy (56 NHL, 28 HD) and 17 patients after therapy of relapse (12 HD, five NHL).

Histology of biopsies was classified according to the WHO classification [7Go] for 61 NHL (16 women, 45 men; aged 44.8±13.7 years), and for 40 patients with classic HD (13 women, 27 men; aged 36±12.9 years). In detail, these were 17 indolent B-cell lymphomas, i.e. 15 nodal lymphomas (12 follicle center and three mantle cell lymphoma) and two extranodal lymphomas (two marginal zone B-cell lymphoma of MALT type), a further 44 aggressive lymphomas, i.e. 34 diffuse large B-cell lymphomas and 10 T-cell lymphomas (five each of anaplastic large cell and peripheral T-cell lymphomas), and finally 23 nodular sclerosis, 13 of mixed cellularity, three lymphocyte-rich and one lymphocyte depletion HD. All patients were staged according to Ann Arbor clinical staging [8Go]. Five patients had stage I, 36 patients had stage II, 27 patients had stage III and 33 patients had stage IV disease. A total of 56 patients presented with B-symptoms and 47 patients had bulky disease.

Chemotherapy of HD patients followed third (HD7-HD9) and fourth (HD10-HD12) generation study protocols of the German Hodgkin-Lymphoma Study Group (GHLSG) [9Go, 10Go]. All but five NHL patients received chemotherapy with either CHOP (cyclophosphamide, vincristine, prednisone, doxorubicin) or VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimens. Radiotherapy was performed in 40 patients with HD and NHL a few weeks after the end of chemotherapy as extended-field (GHLSG protocols HD7 and HD8) or involved-field radiation.

An additional 26 patients (20 NHL, six HD), with partial response (PR) or stable disease (SD) on CT imaging and negative findings on FDG-PET imaging in 24 cases and positive PET findings in two cases, received subsequent salvage therapy without histological confirmation of imaging results and were therefore not considered for evaluation in this study. All patients provided oral or written informed consent after the nature of the imaging studies was fully explained.

Post-treatment evaluation and follow-up
Post-treatment FDG-PET and CT of the neck, thorax and abdomen were analyzed in routine clinical fashion. At the time of image evaluation, the interpreters were unaware of the results of the competitive study.

Median time interval between end of therapy and FDG-PET was 8 weeks (range 1–16) and median time interval between FDG-PET and CT scans was 10 days (range 1–44). Discrepant findings between CT and FDG-PET were verified by biopsy in nine cases and long-term follow-up including surveillance CT scans and other imaging methods as extracted from the patients’ medical files in all other cases. Median follow-up period in patients without relapse was 138 weeks or 32 months (142±53 weeks; range 55–260). Definition of response to treatment followed the suggestions of the Cotswold meeting in HD [11Go] and of the National Cancer Institute International Working Group in NHL [12Go].

CT imaging
CT scans of the neck, thorax and abdomen were performed using a fourth generation helical CT-system (Somatom +4; Siemens AG, Erlangen, Germany). Imaging parameters were 130 kV and 50 mAs for the neck, 130 kV and 40 mAs for the thorax, and 110 kV and 70 mAs for the abdomen. Eighty to 120 ml of intravenous contrast medium was administered using a power injector at a rate of 1–3 ml/s for all imaging studies. One liter of oral contrast was given in four portions for abdominal CT. Axial slices were reconstructed using standard methods. Reconstructed images had a thickness of 5 mm in the neck, 8 mm in the thorax, and 10 mm in the abdomen and pelvis. CT findings were described as complete remission (CR), unconfirmed complete remission (CRu), PR, SD and progressive disease (PD).

PET imaging
Patients fasted for 12 h before the PET study. Baseline glucose was limited below 130 mg/dl (7.2 mmol/l) before FDG injection. FDG-PET studies were performed 100±20 min after intravenous injection of 350–450 MBq of 18F-FDG. Two-dimensional acquisitions were made using a dedicated PET system (Ecat Exact 921/31; Siemens AG) with a 10.8 cm transverse field of view. Seven to 10 bed positions were used to cover the area from the upper neck to the proximal femura. Three- to 8 min transmission and 9 min emission scans were obtained starting from the bladder immediately after urination to minimize bladder activity. Images were reconstructed iteratively by means of an ordered-subset expectation-maximization algorithm and segmented photon-absorption correction [13Go] and reoriented in transverse, coronal and sagittal planes. All foci of elevated 18F-FDG uptake were considered to represent viable lymphoma.

Statistics
The progression-free survival rates were estimated by the Kaplan–Meier method. Equivalence of survival curves was tested with the log-rank test. The Cox proportional hazards model was used to evaluate independent prognostic variables. Comparisons of groups for the probability of relapse and all other comparisons were performed with Fisher's exact test. P <0.05 was considered statistically significant. All analyses were carried out using SPSS for Windows 10.0.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Clinical course of lymphoma patients
A total of 28 lymphoma patients (27.7%) relapsed, eight of them (28.6%) within 3 months of completion of therapy. Median time till relapse was 26 weeks (32±27 weeks; range 4–108). 97 patients (96.0%) were still alive at the time of the last follow-up, three patients had died due to progressive lymphoma and one patient had relapsed but died of a concomitant disease.

Posttreatment evaluation with CT
Post-therapeutic CT indicated CR/CRu in 20 patients (19.8%), PR in 19 (18.8%), SD in 57 (56.4%) and PD in five patients (5%) in a median of 2 months after completion of therapy. Figure 1 shows the Kaplan–Meier progression-free survival estimates in dependence on CT imaging results. The 3-year progression-free survival rates were 100% for patients with CR, 79% for PR, 66.7% for SD and 0% for patients with PD. There was a significant difference in progression-free survival between PD and all other groups (P <0.00001), and between CR and PR (P <0.05) and SD (P <0.005), but not between SD and PR (P=0.281). When differentiating between HD, aggressive NHL and indolent NHL, the 3-year progression-free survival rates in CR patients were 100% for each histologic type, in PR patients the proportions were 90%, 62.5% and 100% for HD, aggressive NHL and indolent NHL, respectively; in SD patients they were 79.0%, 57.7% and 66.7%; and in PD every patient relapsed within 6 months (not shown).



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Figure 1. Kaplan–Meier estimates of progression-free survival in 101 lymphoma patients in dependence on CT imaging results after completion of therapy. Significance values were: CR versus PR, P=0.029; CR versus SD, P=0.004; CR versus PD, P <0.00001; PR versus SD, P=0.281; PR versus PD, P <0.00001; SD versus PD, P <0.00001. CR, complete remission; PR, partial response; SD, stable disease; PD, progressive disease.

 
Only the opposing results of CT imaging, CR and PD, gave a clear-cut estimate of individual prognosis. However, the majority of patients had PR and SD (n=76; 75.3% of all patients), which were consistent with a 20–35% probability of disease progression. Thus it was quite difficult to calculate statistical values such as sensitivity for post-therapeutic CT imaging. Considering PR and SD as negative for lymphoma, sensitivity of CT imaging would be 17.9%, both specificity and positive predictive value would be 100%, negative predictive value 76%, and accuracy would be 77.2%. The analysis of independent variables for disease progression did not classify the results of CT imaging as significant.

Post-treatment evaluation with FDG-PET
Post-therapeutic FDG-PET suggested residual lymphoma tissue in 24 patients (23.8%) in a median of 2 months after chemotherapy or chemo- and radiotherapy. The time interval between a positive PET and documented disease progress in patients not biopsied varied between 6 and 60 weeks (mean 23±17). Figure 2 shows the Kaplan–Meier progression-free survival estimates in dependence on FDG-PET results. The 3-year progression-free survival rates were 89.6% for patients with negative PET and 16.7% for patients with positive PET. This difference was significant (P <0.00001). When differentiating between HD, aggressive NHL and indolent NHL, the 3-year progression-free survival rates in PET negative patients were 94.1% for HD, 86.7% for aggressive NHL and 84.6% for indolent NHL, and in PET-positive patients were 33.3%, 7.1% and 25%, respectively (not shown).



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Figure 2. Kaplan–Meier estimates of progression-free survival in 101 lymphoma patients in dependence on [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) imaging results after completion of therapy. The difference between PET negative (PET–) and PET positive (PET+) was significant (P <0.00001).

 
On a patient basis, the numbers of true-positive, true-negative, false-positive and false-negative results of FDG-PET imaging were 20, 69, four and eight, respectively. Thus, sensitivity of post-therapeutic FDG-PET was 71.4%, specificity was 94.5%, positive predictive value was 83.3%, negative predictive value was 89.6% and accuracy was 88.1%. In detail, four false-positive PET scans occurred in two HD patients Ann Arbor stage IV as well as in one aggressive NHL with Ann Arbor stage II and an International Prognostic Index of 2, and in one indolent NHL with Ann Arbor stage IV. Two of them (one HD, one indolent NHL) had residual activity in mediastinal and iliac lymph nodes when FDG-PET was performed 4 weeks after treatment, the other two (one HD, one aggressive NHL) had increased 18F-FDG uptake in cervical and mediastinal lymph nodes due to a recent infection, which was confirmed clinically. All false-negative PET scans occurred in patients with SD at CT imaging. FDG-PET was performed within 1 month of treatment in seven of the eight false-negative cases, while it was performed after 1 month of treatment in 19 of the 20 true-positive cases. One false-negative PET study, which was performed 3 months after the end of treatment, was obtained in an HD patient with Ann Arbor stage III and SD in axillar and para-aortic lymph nodes, which showed disease progression 2 years later. However, the analysis of independent prognostic factors in Table 1 did not raise evidence for the assumption that the time interval between the end of treatment and the FDG-PET study was of significant importance. Nonetheless, the result of FDG-PET was found to be the most significant independent variable for prediction of disease progression, as shown in Table 1.


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Table 1. Proportional hazards modeling of time to disease progression

 
Combined post-treatment evaluation with CT and FDG-PET
This analysis was performed for all patients who might have been disease-free at the time of the first imaging study after therapy, i.e. 96 patients with CR, PR and SD. Patients who already had PD after therapy were excluded from this comparison; all of them were PET positive. As shown in Figure 3, the 3-year progression-free survival rates were 100% for all patients with CR on CT imaging (n=20) and all patients with PR on CT imaging but negative FDG-PET (n=15). In all, 81.4% of patients with SD on CT but negative PET had a 3-year progression-free survival, which contrasted clearly with patients with a positive PET scan. A positive PET scan was predictive of disease progression in all patients with PR and in 78.6% of patients with SD within 15 months of treatment. The difference between PET-positive and PET-negative PR and SD patients was highly significant (P <0.00001). There was no significant difference between PET-positive PR and SD patients or between PET-negative PR and SD patients. Thus, FDG-PET clearly differentiated patients with PR and SD on CT imaging into low risk for relapse of ≤20% and high risk for relapse of ≥80%.



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Figure 3. Kaplan–Meier estimates of progression-free survival in 96 lymphoma patients without early disease progression in dependence on combined evaluation of CT and [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Significance values were: PR/PET– versus SD/PET–, P=0.081; PR/PET+ versus SD/PET+, P=0.787; PR/PET– versus PR/PET+, P<0.00 001; SD/PET– versus SD/PET+, P <0.00001; PR/PET– versus SD/PET+, P <0.00 001; SD/PET– versus PR/PET+, P=0.0002. CR, complete remission; PR, partial response; SD, stable disease.

 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Ten years ago, an international index and an age-adjusted index were developed to predict survival after chemotherapy in aggressive NHL [14Go, 15Go]. These clinically based pretreatment prognostic indices were further applied to low-grade NHL [16Go]. More recently, the use of molecular profiling was suggested to predict survival after chemotherapy for diffuse large-B-cell lymphoma [17Go]. However, such pretherapeutic measures might be better suited to guide decisions regarding different induction therapies than to predict individual response to a certain therapy [15Go]. For this purpose, a more treatment-related approach might be useful. Often, surveillance CT scan was used to follow-up residual tumor masses and to detect recurrent lymphoma [2Go]. However, the value of CT alone in the follow-up of lymphoma patients is known to be limited [18Go]. Our results suggested that the clinician might find combined interpretation of CT and FDG-PET advantageous for prediction of individual disease progression in the post-therapeutic evaluation of lymphoma patients. While the prognosis of all patients with PD and CR on CT imaging (25% of patients studied) 2 months after completion of treatment could be predicted by means of CT imaging alone, further discrimination with FDG-PET was advantageous for all patients who had PR and SD on CT (75% of patients studied). FDG-PET clearly differentiated patients with PR on CT into those who are likely to relapse within 3 years of treatment and those who are likely to remain in remission. It might be assumed that patients with PR on CT imaging but negative FDG-PET were cured, and should not receive further quality-of-life-constraining therapies. However, this issue should be confirmed in a prospective study. The discrimination capability of FDG-PET was not as clear-cut in patients with SD on CT imaging as it was in patients with PR; nonetheless, progression-free survival in PET-negative patients was 81.4% compared with 21.4% in PET-positive patients, which was also highly significant. The differentiation capability of FDG-PET might be further improved if the number of four false-positive and eight false-negative cases, which all occurred in patients with SD on CT imaging, could be reduced. One reason for a number of false-negative results was a short time interval of <1 month between the end of treatment and the FDG-PET study. A similar observation was recently made by Guay et al. [19Go]. In that study, all false-negative FDG-PET results of a series of 48 HD patients occurred when the time interval between the end of chemotherapy and the PET-scan was shorter than 3 months. It might be assumed that the residual tumor burden shortly after therapy was too small for accurate detection with FDG-PET. Despite the fact that almost all false-negative PET studies were performed within 1 month after treatment and almost all true-positive PET studies were performed later than 1 month after treatment, no significant effect of time interval between the end of therapy and the FDG-PET study could be confirmed by Cox regression analysis in our study.

However, appropriate timing might be even more useful when comparing the predictive value of FDG-PET obtained after the first cycle of chemotherapy [20Go] with that obtained after completion of therapy in our study. No disease progression for 1.5 years was predicted by a negative PET result in only 65% of patients when FDG-PET was performed after the first cycle of chemotherapy [20Go]. This is significantly less than the 89.6% recurrence-free survival observed in our study when FDG-PET was performed after completion of treatment. Even though post-therapeutic FDG-PET was identified as the highest independent prognostic factor, a further improvement of diagnostic accuracy might be achieved by means of coregistered FDG-PET and CT [21Go, 22Go].

Several papers have addressed the prognostic value of post-therapeutic FDG-PET in HD and NHL patients [19Go, 23Go–29Go]. Relapse rates within 2 years after therapy were 76% for PET-positive and 10% for PET-negative patients (P <0.001) in three studies with 168 patients, which did not distinguish between HD and NHL [23Go–25Go]. A differentiation of 48 PET-negative lymphoma patients according to their CT imaging result yielded a higher progression-free survival at 2 years in PET- and CT-negative patients (87%) compared with those with negative PET but positive CT results (60%; P=0.055) [23Go]. In five studies evaluating either HD or NHL patients [19Go, 26Go–29Go], overall relapse rates were 81.5% for PET-positive and 10% for PET-negative HD patients (137 cases) [19Go, 26Go, 27Go], and 100% for PET-positive and 16.5% for PET-negative NHL patients (138 cases) [28Go, 29Go]. These results were largely comparable to those of the single modalities PET and CT in our study. The differentiation between HD, aggressive NHL and indolent NHL in our study revealed only minor differences concerning the predictive value of post-therapeutic FDG-PET. FDG-PET has been evaluated for primary staging of low-grade NHL in 42 patients [30Go] and for detection of disease recurrence in 15 patients [31Go]. These authors observed a significant contribution of FDG-PET to the management of follicular lymphoma but not of other subtypes. In particular, the detection of bone marrow involvement by FDG-PET was reported to be unacceptably low [30Go, 31Go]. A possible explanation might be the limited technical conditions of these studies concerning the lower spatial resolution of the PET scanner used and the lack of attenuation correction. Our data including 17 patients with indolent NHL indicated that FDG-PET might contribute to the treatment evaluation of indolent NHL patients when an adequate imaging technique is used.

A general weakness of this study is the lack of histologic proof in 52 of 61 cases (85%) with discrepant findings between PET and CT. Systematic biopsies of the various sites possibly involved by lymphoma could not be performed for ethical reasons. However, this limitation is inherent to all imaging studies in the field of lymphoma. Another limitation is that ~25% of lymphoma patients with a negative PET scan who were probably cured of their disease received further treatment without histologic confirmation and therefore could not be included in the study. The resulting smaller number of patients and the heterogeneity of subtypes made some subgroup analyses difficult to interpret. Thus, confirmation of our data on a larger number of patients is warranted.

In conclusion, combined evaluation of CT and FDG-PET yielded a more differentiated assessment of individual prognosis of lymphoma patients than the single modalities. HD as well as aggressive and indolent NHL patients destined to progress among those with PR and SD on CT could be differentiated according to post-therapeutic FDG-PET into low risk for relapse of ≤20% and high risk for relapse of ≥80%. A posttherapeutic differentiation of prognostic groups to individualize therapy should therefore include FDG-PET for HD and NHL patients with PD and SD on CT imaging.

Received for publication January 28, 2005. Revision received April 4, 2005. Accepted for publication April 13, 2005.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
1. Rankin SC. Assessment of response to therapy using conventional imaging. Eur J Nucl Med Mol Imaging 2003; 30 (Suppl 1): S56–S64.[Medline]

2. Guppy AE, Tebbutt NC, Norman A, Cunningham D. The role of surveillance CT scans in patients with diffuse large B-cell non-Hodgkin's lymphoma. Leuk Lymphoma 2003; 44: 123–125.[CrossRef][ISI][Medline]

3. Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol 1988; 6: 931–933.[Free Full Text]

4. Shipp MA, Mauch PM, Harris NL. Non-Hodgkin's lymphomas. In DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer. Principles & Practice of Oncology, 5th edition. Philadelphia, PA: Lippincott-Raven 1997; 2165–2220.

5. DeVita VT Jr, Mauch PM, Harris NL. Hodgkin's disease. In DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer. Principles & Practice of Oncology, 5th edition. Philadelphia, PA: Lippincott-Raven 1997; 2242–2283.

6. Weihrauch MR, Dietlein M, Schicha H et al. Prognostic significance of 18F-fluorodeoxyglucose positron emission tomography in lymphoma. Leuk Lymphoma 2003; 44: 15–22.[ISI][Medline]

7. Harris NL, Jaffe ES, Diebold J et al. World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues. Report of the Clinical Advisory Committee Meeting. Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835–3849.[Abstract/Free Full Text]

8. Carbone PP, Kaplan HS, Musshoff K et al. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 1971; 31: 1860–1861.[ISI][Medline]

9. Kogel KE, Sweetenham JW. Current therapies in Hodgkin's disease. Eur J Nucl Med Mol Imaging 2003; 30 (Suppl 1): S19–S27.[Medline]

10. Diehl V, Franklin J, Pfreundschuh M et al. German Hodgkin's lymphoma study group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 2003; 348: 2386–2395.[Abstract/Free Full Text]

11. Lister TA, Crowther D, Sutcliffe SB et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7: 1630–1636.[Abstract/Free Full Text]

12. Cheson BD, Horning SJ, Coiffier B et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. J Clin Oncol 1999; 17: 1244–1253.[Abstract/Free Full Text]

13. Hudson HM, Larkin RS. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 1994; 13: 601–609.[CrossRef][ISI]

14. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993; 329: 987–994.[Abstract/Free Full Text]

15. Shipp MA. Prognostic factors in aggressive non-Hodgkin's lymphoma: who has "high risk" disease? Blood 1994; 83: 1165–1173.[Abstract/Free Full Text]

16. Lopez-Guillermo A, Montserrat E, Bosch F et al. Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma. J Clin Oncol 1994; 12: 1343–1348.[Abstract/Free Full Text]

17. Rosenwald A, Wright G, Chan WC et al. Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 1937–1947.[Abstract/Free Full Text]

18. Rodriguez-Catarino M, Jerkeman M, Ahlstrom H et al. Residual mass in aggressive lymphoma: Does size, measured by computed tomography, influence clinical outcome? Acta Oncol 2000; 39: 485–489.[CrossRef][ISI][Medline]

19. Guay C, Lepine M, Verreault J, Benard F. Prognostic value of PET using 18F-FDG in Hodgkin's disease for posttreatment evaluation. J Nucl Med 2003; 44: 1225–1231.[Abstract/Free Full Text]

20. Kostakoglu L, Coleman M, Leonard JP et al. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med 2002; 43: 1018–1027.[Abstract/Free Full Text]

21. Schöder H, Larson SM, Yeung HW. PET/CT in oncology: integration into clinical management of lymphoma, melanoma, and gastrointestinal malignancies. J Nucl Med 2004; 45 (Suppl 1): 72S–81S.[ISI][Medline]

22. Schaefer NG, Hany TF, Taverna C et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging: Do we need contrast-enhanced CT? Radiology 2004; 232: 823–829.[Abstract/Free Full Text]

23. Jerusalem G, Beguin Y, Fassotte MF et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999; 94: 429–433.[Abstract/Free Full Text]

24. Cremerius U, Fabry U, Neuerburg J et al. Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma. Nuklearmedizin 2001; 40: 23–30.[ISI][Medline]

25. Naumann R, Vaic A, Beuthien-Baumann B et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol 2001; 115: 793–800.[CrossRef][ISI][Medline]

26. Weihrauch MR, Re D, Scheidhauer K et al. Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood 2001; 98: 2930–2934.[Abstract/Free Full Text]

27. Spaepen K, Stroobants S, Dupont P et al. Can positron emission tomography with 18F-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity? Br J Haematol 2001; 115: 272–278.[CrossRef][ISI][Medline]

28. Spaepen K, Stroobants S, Dupont P et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (18F-FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: Is 18F-FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001; 19: 414–419.[Abstract/Free Full Text]

29. Mikhaeel NG, Timothy AR, O'Doherty MJ et al. 18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin's Lymphoma—comparison with CT. Leuk Lymphoma 2000; 39: 543–553.[ISI][Medline]

30. Jerusalem G, Beguin Y, Najjar F et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL). Ann Oncol 2001; 12: 825–830.[Abstract]

31. Najjar F, Hustinx R, Jerusalem G et al. Positron emission tomography (PET) for staging low-grade non-Hodgkin's lymphomas (NHL). Cancer Biother Radiopharm 2001; 16: 297–304.[CrossRef][ISI][Medline]





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