Introduction

Over the last 2–3 decades, we have seen substantial improvements in the prognosis of patients with lymphoma [1]. These improvements can be attributed to the following factors:

  1. 1.

    Better understanding of the biology of the diseases and advances in molecular pathology, leading to better disease characterization and identification of valuable prognostic markers as well as therapeutic targets.

  2. 2.

    Improved treatment regimens, notably the introduction of granulocyte growth factors, monoclonal anti-CD20 antibodies, and high-dose chemotherapy with autologous stem cell support.

  3. 3.

    Better imaging methods with cross-sectional images providing more accurate staging and response assessment, and the more recent introduction of functional imaging, notably positron emission tomography (PET) and PET/computerized tomography (CT), which is now the cornerstone of lymphoma imaging.

The introduction of CT in the 1980s resulted in improved staging accuracy and CT replaced cumbersome staging procedures such as lymphangiography and staging laparotomy. The introduction of CT was not based on much evidence, as opposed to the more than 1000 studies investigating PET and PET/CT in lymphoma. During the last 15 years, a large number of studies have shown superior accuracy and sensitivity of PET/CT over CT. Along with patient symptoms and clinical examination, CT and PET/CT are now the cornerstones of the assessment of lymphoma patients. The recent international guidelines for imaging in the staging and response assessment of lymphoma recommend PET/CT for staging and response assessment of Hodgkin lymphoma (HL) and most non-Hodgkin lymphoma (NHL) subtypes [2, 3]. The only PET tracer in widespread clinical use for lymphoma is still 2-[18F]fluor-2-deoxyglucose (FDG). In the following and if not otherwise specified, PET refers to FDG-PET and PET/CT refers to FDG-PET/CT.

PET and PET/CT for early treatment monitoring and response-adapted therapy

A number of well-established pre-treatment prognostic factors have been shown to predict survival in large cohort studies of lymphoma patients [4–7]. These prognostic factors are used along with the clinical stage to determine the initial treatment strategy. However, in both indolent and aggressive lymphoma, the tumor response to induction treatment is an important surrogate for other measures of clinical benefit from the treatment, including progression-free and overall survival. A reliable and early prediction of response to therapy can possibly separate good-risk patients who will be cured with conventional therapy or even less intensive and less toxic regimens from poor-risk patients for whom an early switch to alternative, more aggressive treatment strategies could improve the likelihood of remission and cure. This concept called risk-adapted therapy is widely recognized as a potential way to achieve higher cure rates with lower or equal risk of treatment-related morbidity and mortality.

Conventional methods for treatment response monitoring are based on morphological criteria, and a reduction in tumor size on CT is the most important determinant [8–10]. However, size reduction is not necessarily an accurate predictor of outcome. But even more importantly, tumor shrinkage takes time and depends on a number of factors in the host. So the rate of structural regression cannot form the basis for therapy response assessment until rather late during treatment, at which point a treatment modification might be less useful.

As opposed to the morphological changes of the lymphoma occurring later during therapy, functional imaging with FDG-PET enables evaluation of the metabolic changes that take place very early during the treatment induction. Several studies of FDG-PET after 1–4 cycles of chemotherapy in aggressive lymphomas and follicular lymphoma (FL) [11–19] have shown that these early metabolic changes are highly predictive of final treatment response and progression-free survival (PFS). However, treatment-induced inflammation and concomitant infections may lead to false-positive interim scans, and this risk is particularly pertinent in patients treated with intensive regimens [20]. Most evidence is available for performing early interim FDG-PET after 2–4 cycles of chemotherapy. However, some studies strongly suggest that the predictive value may be as high after only one cycle of chemotherapy [15, 19]. This is of importance for early PET response-adapted treatment regimens, since the treatment adaptation is best performed as early as possible to increase the chance of satisfactory remission and to avoid unnecessary ineffective chemotherapy.

Interim treatment monitoring is more a tradition than an evidence-based practice. Even though it is well established that continued treatment in patients with progression or no response during first-line therapy will invariably lead to treatment failure, the widespread use of CT for treatment monitoring has never been proven to improve the outcome of lymphoma patients. This is true for PET/CT imaging as well, and until we have data from the studies of PET response-adapted therapy, interim imaging should only be performed if clinically justified. The recently revised lymphoma imaging recommendations state that PET–CT is superior to CT alone to assess early response, if such an assessment is needed, but changing therapy solely on the basis of interim PET–CT is not recommended, unless there is clear evidence of progression. It is recommended that both interim and post-treatment PET scans are interpreted and reported according to the Deauville 5-point scale (Table 1) [2]. Figure 1 shows examples of PET images with response scored using the 5-point scale.

Table 1 The Deauville 5-point scale for PET response in lymphoma
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Fig. 1
figure 1

Examples of baseline and interim PET images with response assessed according to the Deauville 5-point scale

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Interim PET in HL

Several studies of FDG-PET after 1–3 cycles of chemotherapy [21–25] have shown that these early metabolic changes are highly predictive of final treatment response and PFS. Most evidence is available for FDG-PET after two cycles of chemotherapy. However, there are data to suggest that the prognostic accuracy is very high already after only one cycle of chemotherapy, and that the negative predictive value (NPV) may be higher [19].

A retrospective analysis of 88 patients scanned after two or three cycles of ABVD-like chemotherapy (ABVD = adriamycin, bleomycin, vinblastine and dacarbazine) for HL showed a 5-year PFS of 39 % in the PET-positive group compared with 92 % in the PET-negative group [21]. These results were later confirmed in several prospective studies [22–24], showing excellent outcomes for early PET-negative patients (app. 95 % long-term PFS) and rather poor outcomes for early PET-positive patients. In patients with advanced disease, the high prognostic value of early FDG-PET overshadows the role of the IPS [22, 25]. The prognostic value of PET/CT in advanced HL was recently validated by Gallamini et al., who showed 3-year failure-free survival of 28 and 95 % for early PET-positive and early PET-negative patients, respectively [26]. In this international validation study, the inter-observer agreement was very high between six independent PET/CT reviewers [27], using the Deauville criteria for interim PET which have become widely recognized [28]. Also using the Deauville criteria, and in a prospective study with blinded, central review, Hutchings and coworkers recently showed that the NPV of interim PET is higher after one cycle of ABVD than after two cycles of ABVD, suggesting that interim scanning should be performed very early in situations where a high NPV is desired, such as strategies where de-escalation of chemotherapy or omission of radiotherapy is offered to early PET-negative patients [29].

The role of early interim PET in limited stage HL has been a little unclear since the aforementioned studies focused mainly on patients with advanced-stage disease, and since most of the ability to predict progression was derived from events occurring in advanced-stage patients. However, two recently published retrospective studies have shown that the prognostic value of early interim PET is indeed strong in the early stage as well as in advanced-stage HL patients [30, 31]. As might be expected due to the lower a priori risk of relapse and the use of radiotherapy in most patients, the positive predictive value of early interim PET was lower than in patients with advanced-stage disease.

The positive predictive value of early FDG-PET seems to be lower in patients treated with the more dose-intensive BEACOPPesc regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) than in patients treated with ABVD [32]. Also, the positive predictive value is lower in patients with early stage HL, probably due to both the inherent better prognosis for this patient group and due to the subsequent radiotherapy which may in many early stage patients overcome an insufficient chemotherapy response [22, 23].

PET response-adapted HL therapy

More than 90 % of early stage HL patients are cured with standard therapy. But the patients still have a dramatically reduced life expectancy due to treatment-related illness including second cancers and cardiopulmonary disease. In fact, early stage HL patients more often die from late effects of therapy than from the disease itself [33]. This suggests that a substantial number of early stage HL patients are subject to some amount of over-treatment, and it is the background for using early PET/CT to identify good-risk early stage patients eligible for less intensive treatment. A number of trials investigate such PET response-adapted therapy in early stage HL. The now completed UK National Cancer Research Institute (NCRI) Lymphoma Group RAPID trial for early stage patients as well as the still ongoing German Hodgkin Study Group (GHSG) HD16 protocol investigates the non-inferiority of reducing treatment intensity by omitting radiotherapy to interim PET-negative early stage patients. The experimental arms of the EORTC/GELA/IILFootnote 1 H10 protocol also omitted radiotherapy to PET-negative patients while escalating to BEACOPPesc followed by radiotherapy in PET-positive patients. In other words, this trial tests the non-inferiority of a less toxic treatment to good-risk patients, while at the same time attempting treatment intensification for patients regarded as having a high risk of failure based on a positive interim PET/CT. Both the RAPID trial and the H10 trial failed to demonstrate a non-inferiority of the no-radiotherapy strategy in early PET-negative patients, but the outcome for patients was excellent regardless of whether radiotherapy was given or not. Interestingly, the H10 study showed superior PFS for patients with treatment intensification to BEACOPPesc in case of a positive PET after two cycles of ABVD.

Around 70 % of advanced-stage HL patients are cured with 6(–8) cycles of ABVD with or without consolidation radiotherapy, which is first-line therapy in most centers. BEACOPPesc cures 85–90 % of patients if given upfront, but serious concerns regarding acute toxicity and second myeloid neoplasias are the reason why many centers in Europe and North America are very reluctant to use this regimen as standard therapy [34]. A number of trials investigating PET response-adapted therapy for advanced-stage HL patients are ongoing. A number of non-randomized trials use early treatment intensification with BEACOPPesc (Italian GITIL trial and the RATHL trial)Footnote 2 or even ASCT (Italian FIL trial) in patients who are still PET-positive after two cycles of ABVD. The randomized German GHSG HD18 trial tests abbreviation of BEACOPPesc therapy based on PET results after two therapy cycles. The French AHL 2011 trial is also a BEACOPPesc-based randomized trial with treatment modifications based of PET after both two and four cycles. Recently presented results from the RATHL study demonstrated, in patients achieving a negative PET after two cycles of ABVD, that omission of Bleomycin in the remaining four treatment cycles can be safely done [35].

Interim PET in indolent NHL

There is a relative paucity of data on the value of interim FDG-PET in indolent lymphomas. Bishu et al. reported a retrospective series of 31 patients with advanced-stage FL, of whom 11 had FDG-PET scans midway through four cycles of induction chemotherapy. The number of patients was too small for any firm conclusions. Still, the results showed interesting differences: Four patients with some persistent FDG uptake had a mean PFS of 17 months and seven interim PET-negative patients had a mean PFS of 30 months [36]. In a prospective study of 121 FL patients treated with R-CHOP chemotherapy, Dupuis et al. found a clear prognostic value of PET performed after four cycles and after the end of the treatment. After central PET review and with a median follow-up of 23 months, 2-year PFS rates were 86 % for interim PET-negative versus 61 % for interim PET-positive patients (P = 0.0046) and 87 % for final PET-negative versus 51 % for final PET-positive patients (P < 0.001), respectively. Two-year overall survival also significantly differed according to final PET results: 100 versus 88 % (P = 0.0128) [37]. There are only case reports on the value of interim FDG-PET in localized FL or the more uncommon subtypes of indolent NHL, such as marginal zone lymphoma and small lymphocytic lymphoma.

Even if a clear correlation between interim FDG-PET and treatment outcome is shown in the future, the clinical implications are uncertain, since advanced-stage indolent lymphoma is very different from aggressive NHL. First of all, current first-line therapies for advanced-stage FL are not curative, and it is unclear if early treatment intensification with autologous stem cell transplant (ASCT) or allogeneic bone marrow transplantation is of any benefit to poor-risk patients. Secondly, the long natural history of FL and the relative success of subsequent treatment lines in inducing lasting remissions mean that a longer time to first progression does not necessarily translate into longer survival.

Interim PET in aggressive NHL

In aggressive NHL, PFS ranges from 10 to 50 % at 1 year for early PET-positive patients and from 79 to 100 % at 1 year for early PET-negative patients. The high risk of relapse seen among PET-positive patients is consistently shown in both early and advanced stages. Mikhaeel et al. studied a large cohort of 121 high-grade NHL patients, retrospectively and with a median follow-up of 28.5 months. They confirmed that response on FDG-PET after two or three cycles strongly predicts PFS and OS. Estimated 5-year PFS was 89 % for the PET-negative group, 59 % for patients with minimal residual uptake (MRU) on FDG-PET, and 16 % for the PET-positive group. Survival analyses showed strong associations between early FDG-PET results and PFS and OS [17]. Haioun et al. prospectively studied 90 patients with aggressive NHL, performing FDG-PET after two cycles of chemotherapy. They similarly found 2-year PFS rates of 82 and 43 % in early PET-negative and early PET-positive patients, respectively, and 2-year OS rates of 90 and 60 % [18]. Spaepen et al. compared interim FDG-PET after two cycles of chemotherapy with the International Prognostic Index (IPI). In multivariate analysis, FDG-PET at mid-treatment was a stronger prognostic factor for PFS and OS than the IPI (P < 0.58 and P < 0.03, respectively) [13]. A number of other more recent studies have investigated the value of interim PET specifically in DLBCL cohorts and found NPVs similar to those found in the above-mentioned studies of mixed aggressive NHL populations. But the positive predictive value is variable and generally poor [38, 39]. A possible explanation for the low-positive predictive value in aggressive NHL cohorts is the higher risk of inflammation and infections among patients who are treated with the more dose-dense and dose-intensive NHL regimens, as mentioned above, as well as with rituximab which causes immunosuppression due to B cell depletion. To overcome the low-positive predictive value of interim PET, some investigators have proposed a semi-quantitative approach (relative or absolute change in SUV from baseline to interim scan) as superior to visual PET assessment in patients with DLBCL [40, 41].

Aggressive NHL covers a number of lymphoma subtypes where first-line treatment of both localized and advanced disease stages is given with a curative intent. Aggressive NHL patients who respond poorly to first-line treatment or relapse soon afterward generally have a very poor prognosis even with high-dose salvage regimens. Such poor-risk patients could benefit from having their treatment failure recognized early during first-line therapy to switch a more intensive regimen as soon as possible. Much inspired by a similar and more widespread trend in HL, a number of trials are currently investigating early PET response-adapted treatment strategies. Most studies test whether early or mid-treatment PET-positive patients with aggressive NHL (mainly DLBCL) will benefit from early escalation to more intensive regimens or even high-dose therapy with autologous stem cell support (ASCT) [42–45]. The German PETAL study failed to show benefit for patients with a poor response on PET (<66 % change in maximum SUV) after two cycles of R-CHOP to a more intensive Burkitt type regime [46], and similarly a Canadian study which escalated PET-positive patients after four cycles of R-CHOP to more intensive treatment with R-ICE reported that relatively few PET-pos pts converted to a negative PET scan following R-ICE [47]. One de-escalation study compares standard treatment with six cycles R-CHOP to good-risk DLBCL patients to abbreviated therapy with four cycles R-CHOP in patients with a negative PET after two cycles of therapy [48].

PET/CT for post-therapy response evaluation of lymphomas

Response to treatment serves as an important surrogate for other measures of clinical benefit such as progression free and overall survival. Response is also an important guide in decisions regarding continuation or change of therapy. Until recently, response evaluation in lymphoma was done according to the International Workshop Criteria [49], based mainly on morphological evaluation with a reduction in tumor size on CT being the most important factor. But after completion of therapy, CT scans will often reveal residual masses and the presence of such masses is not highly predictive of outcome. By conventional methods, it is very difficult to assess whether this represents viable lymphoma or fibrotic scar tissue. An extensive number of studies have shown that FDG-PET performed post-treatment is highly predictive of PFS and OS in NHL patients with and without residual masses on CT [50, 51]. Since the International Harmonization Project included PET in the response criteria for aggressive malignant lymphomas in 2007 [52], a number of retrospective analyses have confirmed the superiority of PET-driven response evaluation in HL compared with morphological imaging alone [51, 53]. The data on indolent NHL are based on fewer studies [54–56], but both the already cited prospective study by Dupuis et al. and a retrospective study by Luminari et al. show that end-of-treatment PET is the strongest prognostic factor in multivariate analysis to predict survival [37, 57]. As already mentioned, the most recent revision of the international guidelines for imaging and response evaluation of lymphoma, the Lugano Classification, has PET/CT as the cornerstone in response evaluation of all FDG-avid malignant lymphomas [2, 3].

In advanced-stage HL, radiotherapy has until recently been frequently given to residual masses. In this situation, PET/CT may help in discriminating between a residual mass with viable lymphoma cells and a residual mass consisting only of fibrotic tissue. However, since PET/CT cannot detect microscopic disease, it has not been entirely clear whether a PET-negative residual mass requires radiotherapy or not. The mature results of the German HD15 trial shed light on this for patients treated with BEACOPP regimens. In this study, consolidation radiotherapy was given only to patients with a PET-positive residual mass of more than 2.5 cm. The remaining majority of patients who did not receive radiotherapy had a relapse-free survival of 94 % after 1 year, indicating that radiotherapy can be safely omitted in advanced-stage HL patients who are PET negative after the end of BEACOPPesc [58]. The situation is a little less clear for ABVD-treated patients. However, a retrospective analysis from the British Columbia Cancer Agency was presented at the Annual Meeting of the American Society of Clinical Oncology in 2011. This retrospective study reported a 5-year experience where patients with residual masses >2 cm after chemotherapy underwent PET/CT (n = 163). Only patients with a positive post-treatment PET/CT received radiotherapy. Of the patients with a negative PET/CT (n = 130, 80 %), the 3-year PFS was 89 % with a median follow-up of 34 months, as opposed to the PET-positive patients who had a 3-year PFS of 55 % despite receiving radiotherapy [59]. These results support the omission of radiotherapy to advanced-stage HL patients who receive a PET-negative remission after six cycles of chemotherapy.

Unlike in HL, the role of post-treatment PET/CT for selection of NHL patients for consolidation radiotherapy is unclear. Based on promising data showing a very high NPV of PET/CT in primary mediastinal B cell lymphoma [60], the International Extranodal Lymphoma Study Group conducts an experimental approach where consolidation radiotherapy is given only to patients with a PET-positive residual mass [61]. Also, the British Columbia Cancer Agency has since 2005 routinely used with post-chemotherapy PET for all patients with residual masses larger than 2 cm. Only PET-positive patients receive consolidation radiotherapy. With 262 patients included in the series and a median follow-up of 45 months, only one of 179 PET-negative patients has received radiotherapy. The 4-year PFS and OS are 74 and 83 %, respectively. Since the data have still only been presented in abstract form, it is unfortunately unclear if the relapses were predominantly located within or outside the sites of residual disease. If most relapses occur outside the sites of residual disease, there seems to be little value of consolidation radiotherapy in PET-negative patients, but this is not quite so clear if a substantial number of relapses are seen within the sites of residual disease after first-line treatment [62].

Disease surveillance after first remission

Aggressive non-Hodgkin lymphomas

The value of routine surveillance imaging in aggressive NHL in first remission is controversial. Despite the lack of evidence surveillance imaging is often performed with regular intervals during the first years in remission. The rationale behind this may be a presumed better outcome in patients with early and asymptomatic relapse as compared to those patients presenting with overt lymphoma symptoms. Early detection of relapse could in theory be advantageous for following reasons: (1) lower tumor burden at relapse (and maybe reduced tumor heterogeneity and prevention of treatment resistant clones), and (2) less disease-related impairment of function and organs with better tolerability of treatment. Low disease stage and ECOG performance status 0–1 at relapse are associated with a better outcome in DLBCL [63]. With less than a quarter of the relapses being imaging detected, routine imaging did not contribute significantly to relapses detection in studies based on imaging modalities less sensitive than PET/CT [64–68]. Furthermore, the number of scans per relapse exceeded 100 per preclinical relapse for both DLBCL and peripheral T cell lymphomas in first complete remission and out of all patients in complete remission entering intensive follow-up protocols only a very small minority (2–3 %) will experience imaging-detected relapse [68]. Few studies have investigated the value of PET/CT in the surveillance of aggressive NHLs, mainly reporting on DLBCL. Generally, the rate of imaging-detected relapse seems to be higher when using regular PET/CT surveillance in first remission and depending on the surveillance protocol 31–100 % of relapses were detected by imaging [69–71]. However, with the number of PET/CT scans per relapse ranging between 35 and 120 [71, 72] and an estimated cost of up to 85,550 USD per preclinical PET/CT detected relapse, an indiscriminate use of PET/CT surveillance is not likely to be cost effective. Restricting the use of PET/CT to high-risk patients (IPI > 2) decreases the number of PET/CT scans per relapse to 22 and may tip the balance toward better cost effectiveness [71]. In patients with transformed indolent lymphomas undergoing routine imaging with PET/CT at least one time during follow-up, the PET/CT detected relapses were all indolent histologies and less important from a clinical perspective. On the contrary, cases of relapsed DLBCL were symptomatic [73]. Since FDG uptake is non-specific and not restricted to lymphoma recurrence, the PPV of PET/CT surveillance in aggressive NHLs has been reported as low to moderate with values between 21 and 60 % [69, 71, 74]. The increasing use of PET/CT for lymphoma has probably led to safer recognition of uptake patterns characteristic for lymphoma and hence less false-positive reporting. Still, a confirmatory biopsy of lymphoma suspicious findings on PET/CT is mandatory whenever possible. As opposed to the problematic PPV of PET/CT, the NPV has been reported as uniformly high and often 100 % [69, 71, 75]. This means that a negative PET/CT study virtually rules out recurrent disease and the need for further investigations in patients with symptoms suggesting lymphoma relapse. Finally, the use of routine surveillance imaging in aggressive NHLs can only be justified if early relapse detection is associated with improved survival. Some studies have suggested that imaging-detected relapse of aggressive NHL could be associated with improved outcome, whereas others found no difference in outcome [66, 68, 71]. However, the retrospective design of these studies does not allow firm conclusions about the causal role of imaging due the presence of important bias (lead time, length time and guarantee time).

Indolent non-Hodgkin lymphomas

While use of routine imaging in the follow-up of aggressive NHLs is still widespread, the use of routine imaging in the follow-up of indolent NHLs is not recommended. An observational approach without initial treatment is often chosen for patients with an asymptomatic relapse of an indolent lymphoma. An exception could be specific cases where an asymptomatic relapse could lead to unrecognized compression of vital organs such as vascular structures. In any case, PET/CT has no role in this setting.

Hodgkin lymphoma

Like in NHL, the value of routine follow-up imaging in HL is low. Conclusions from previous studies support a restrictive use of routine surveillance imaging, as the majority of relapses are preceded by symptoms or abnormalities on clinical examination, but these studies mainly used conventional radiograms and not whole-body CT, which is now more commonly performed [76, 77]. Routine CT surveillance, however, also appears to have limited value; in a study by Dryver et al., only 9 % of HL relapses were diagnosed by CT [78]. More recent studies of HL patients in remission after first-line therapy who underwent routine PET/CT follow-up imaging have shown a very low-positive predictive value and poor cost effectiveness [75, 79, 80]. Interestingly, a recent randomized trial of surveillance strategies in HL showed that the use of chest X-ray and ultrasound was just as effective as PET/CT in early relapse detection, but at a much lower cost and with higher PPV [81].

Response prediction with FDG-PET before high-dose salvage therapy

Duration of remission prior to relapse, and the response to induction therapy are important prognostic factors that predict a good outcome after high-dose chemotherapy with autologous stem cell support (HD+ASCT) [82, 83]. A number of studies have shown that PET/CT performed after induction therapy and before HD+ASCT can predict which HL patients will achieve long-term remission after the salvage regimen for relapsed HL [84–86] and NHL [87–92]. These studies all report a poor long-term PFS (after 2–5 years) in patients who are PET-positive after induction chemotherapy (31–41 %), compared to a PFS of 73–82 % in the patients who reach a PET-negative remission before HD+ASCT. However, these studies also report a higher false-positive rate than with PET/CT performed early during first-line therapy. The role of PET/CT in this setting is still unclear, but the available evidence calls for clinical trials to improve the outcomes for patients who are still PET positive after induction salvage chemotherapy. Encouraging results were published recently by Moscowitz et al., who showed that a PET-guided approach may indeed help these patients. In this study, patients who were still PET-positive after the standard induction regimen (ICE) were not taken to HD+ASCT but instead given a non-cross-resistant regimen consisting of four biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) before HD+ASCT. Those patients who converted to PET-negative after GVD and before HD+ASCT had similar outcomes as those who were PET negative after ICE and went on with the initially planned HD+ASCT [93].

Conclusions and recommendations

Supported by a large number of studies and in line with the recent consensus recommendations for lymphoma imaging as well as the revised criteria for lymphoma staging and response evaluation, PET/CT is recommended for staging and post-treatment response assessment of all FDG-avid lymphomas [2, 3]. There are sufficient data to support the use of interim PET for treatment monitoring when interim imaging is appropriate. CT is still the preferred imaging method for non-FDG-avid lymphomas, as well as for selected cases where routine surveillance imaging is considered necessary. For interim and post-treatment imaging, the Deauville 5-point scale is recommended for interpretation and reporting of PET results. The use of interim PET imaging to guide therapeutic decisions is in evolution and data are still emerging from clinical trials. Semiquantitative and quantitative PET assessments (SUV, MTV, TLG) are promising but their role is still to be defined. Currently, much effort is put into the standardization of PET/CT methodology and interpretation, making the results of trials more comparable and ensuring a better translation into clinical practice. Upcoming results of interim PET response-adapted therapy trials are likely to impact on the management of de-novo and relapsed lymphoma patients in the near future.