Charles Mesguich

Hodgkin lymphoma: a negative interim-PET cannot circumvent the need for end-of-treatment-PET evaluation

We examined the outcome of a cohort of patients with Hodgkin lymphoma (HL) in order to assess if fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) at the end of treatment (end‐PET) can be omitted when the interim PET (int‐PET) is negative. Seventy‐six ABVD(adriamycin, bleomycin, vinblastine, dacarbazine)‐treated patients were retrospectively included. No change in treatment was made on the basis of int‐PET results. Suspicious foci on end‐PET received biopsy confirmation whenever possible. Median follow‐up was 58·9 months. Uptake on int‐PET higher than liver (scores 4–5) was rated positive according to the Lugano classification, while a positive end‐PET corresponded to scores 3, 4 and 5. Fifteen patients had treatment failure. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy of int‐PET were 46·7%, 85·2%, 43·8%, 86·7% and 77·6%, respectively. For end‐PET the figures were: 80%, 93·4%, 75%, 95% and 90·8%. Eight patients with negative int‐PET had treatment failure; six of them were identified as non‐responders with end‐PET. The 5‐year progression‐free survival (PFS) was 87% for patients with negative int‐PET versus 56% with positive int‐PET. The 5‐year PFS was 96% with negative end‐PET versus 23% with positive end‐PET. The prognostic information from int‐PET as regards PFS (log‐rank test P = 0·0048) was lower than that provided by end‐PET (P < 0·0001). Int‐PET predicted only half of the failures. When used in clinical routine, a negative int‐PET study cannot obviate the need for end‐PET examination.

Role of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in post-treatment evaluation of anal carcinoma

The aim of this study was to evaluate the relevance of PET/CT and 18F-FDG as a strategy for response evaluation after chemoradiotherapy for anal cancer. For this, the performance of posttreatment 18F-FDG PET/CT, the impact on patient care, and the predictive value of metabolic response were assessed. Methods: This was a retrospective and multicenter analysis of 87 patients treated by chemoradiotherapy for anal squamous cell carcinoma between October 2007 and October 2013. All patients underwent systematic posttreatment 18F-FDG PET/CT and were followed with at least a clinical examination every 4 mo for 2 y and every 6 mo thereafter. Disease progression was confirmed by biopsy for all patients in the case of local recurrence before surgery. Kaplan–Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and progression-free survival (PFS) or cause-specific survival (CSS). Results: The median follow-up was 25 mo. 18F-FDG PET/CT was performed 1–8 mo (median, 4 mo) after completion of chemoradiotherapy. Overall, 25 patients relapsed and 13 died. The posttherapy 18F-FDG PET/CT did not show any abnormal 18F-FDG uptake (complete metabolic response [CMR]) in 55 patients whereas 32 displayed incomplete response (non-CMR): 15 patients with partial response and 17 with disease progression. The sensitivity of 18F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%–97%), specificity was 85% (95% CI, 75%–92%), positive predictive value was 72% (95% CI, 61%–90%), and negative predictive value was 96.4% (95% CI, 90%–98.7%). The 2-y PFS was 96% (95% CI, 90–100) for patients with CMR and 28% (95% CI, 14–47) for non-CMR patients (P < 0.0001). The 2-y CSS was 100% for patients with CMR and 59% (95% CI, 42–84) for those without CMR (P < 0.0001). 18F-FDG PET/CT changed patient management in 14 cases (16%), with relevant modifications in 12 (14%). A Cox proportional hazards model of survival outcome indicated that a CMR was the only significant predictor of PFS and CSS (P < 0.0001). Conclusion: 18F-FDG PET/CT shows good accuracy in posttreatment evaluation of anal cancer and has a relevant impact on patient management. Moreover, CMR is associated with good survival outcome. Thus, 18F-FDG PET/CT may play a significant role during posttreatment follow-up of anal cancer.

Advanced Hodgkin’s lymphoma: End-of-treatment FDG-PET should be maintained

Positron emission tomography with F–fluorodeoxyglucose (FDG-PET) has become a cornerstone procedure in the modern management of Hodgkin’s lymphoma (HL) [1–4]. It offers better initial staging and risk stratification [3]. FDG-PEToften detects occult extranodal disease, notably focal bone marrow lesions [5–7]. It rendered useless routine bone marrow biopsy [3]. HL is associated with a high rate of residual masses at the end of therapy, which are difficult to characterize as residual disease or not on conventional imaging. Therefore, a major milestone was the finding that end-of-treatment FDG-PET offers excellent prediction of progression-free-survival (PFS), even in the presence of a residual mass [8–11]. This finding led to the introduction of FDG-PET imaging in response criteria for HL [12]. More recently, FDG-PET performed early during chemotherapy (interim-PET) has been used to tailor treatment. Here, we comment on results of two recently published prospective multicentre trials in which patients with advanced HL had response-adapted therapy based on interim-PET [13, 14]. These trials were triggered by observational studies showing high prognostic accuracy of interim PET [15]. For example, in one retrospective multicenter study of patients with advancedstage or early unfavorable HL, the 3-year PFS for patients with positive interim-PETafter two cycles ofABVD (score≥ 4 on the Deauville 5-point scale) was 28% and for patients with negative interim-PET 95.0% (P < .0001) [16]. In the Southwest Oncology Group (SWOG) S0816 phase II study, which included stages III and IV HL, interim PETpositive patients after two cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) were switched to escalated-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone). The 2-year PFS in interim PET-positive patients was 64% [13]. Again, in the RATHL study (stage II unfavorable, stage III and stage IV), the 3-year PFS in interim PETpositive patients who were switched from ABVD to a BEACOPP regimen was 67.5% [14]. These results are very encouraging as they show that interim PET allows a finely tuned treatment by restricting the use of BEACOPP to the 15% to 20% of patients who are PET-positive. BEACOPP offers higher cure rates in HL, but is also associated with a higher percentage of short-term and long-term adverse effects (hematologic toxicity, infections, infertility, secondary malignancies) [17]. In the absence of randomisation, the extent of benefit from switching to BEACOPP cannot be assessed from these trials [13, 14]. Also, the optimal strategy in these interim-PET-positive patients might evolve in light of the new therapeutic arsenal (targeted therapy, checkpoint inhibitors such as anti-PD-1 therapy, etc.) that is now available; for example, the possibilities of combining chemotherapy and targeted therapy with the anti-CD30 antibody-drug conjugate brentuximab vedotin [18]. Surprisingly, in both trials, the relapse rates in patients with a negative interim-PET were much higher than the rates expected from historical data [16]. In the SWOG S0816 study, which included only advanced stages, the 2-year PFS in interim PET-negative patients was 82% [13]. In the RATHL study, in which 42% of patients had stage-II disease, the 3-year PFS in interim PET-negative patients who continued on ABVD was 85.7% [14]. The outcome was influenced by initial riskgroup: 3y–PFS was 90% in stage II patients with adverse risk, * Elif Hindié elif.hindie@chu-bordeaux.fr

New Perspectives Offered by Nuclear Medicine for the Imaging and Therapy of Multiple Myeloma.

The management of multiple myeloma has fundamentally changed over the years and imaging techniques able to match the therapeutic advances are now much needed. Although many patients now achieve complete response after first-line treatment, relapse is common. Therefore, it would be important to improve the initial prognostic stratification and to detect minimal residual disease after treatment. 18F-FDG-PET/CT is a useful imaging tool which has a high prognostic value at baseline evaluation and can effectively differentiate active from inactive lesions during induction treatment or after autologous stem-cell transplantation. In combination with biological data, it improves the prediction of relapse. Other PET tracers may soon enter clinical practice and overcome some of the limitations of 18F-FDG, such as the low sensitivity in detecting early bone marrow infiltration. Excellent results with 11C-Methionine are reported by Lapa and colleagues in this issue of the Journal. 11C-Methionine uptake reflects the increased protein synthesis of malignant plasmocytes and correlates well with bone marrow infiltration. Other promising PET ligands include lipid tracers, such as 11C-Choline or 11C-acetate, and some peptide tracers, such as 68Ga-Pentixafor, that targets CXCR4 (chemokine receptor-4), which is often expressed with high density by myeloma cells. Malignant plasma cells are radiosensitive and thus potentially amenable to systemic radionuclide therapy. Indeed, excellent preclinical results were obtained with radioimmunotherapy targeting CD38. Also, preliminary clinical results with peptides targeting CXCR4 (e.g. 177Lu- or 90Y-Pentixather) are encouraging. Multiple myeloma may represent a renewal of the already strong partnership between hematologists and nuclear medicine physicians.

Infections in patients using ventricular-assist devices: Comparison of the diagnostic performance of 18 F-FDG PET/CT scan and leucocyte-labeled scintigraphy

BackgroundThe usage of left-ventricular-assist device (LVAD) is increasing in patients presenting with advanced heart failure. However, device-related infections are a challenge to recognize and to treat, with an important morbidity and mortality rate. The role of nuclear medicine imaging remains not well established for LVAD infections. The present study compared the accuracy of positron emission tomography/computed tomography with 18F-fludeoxyglucose (18F-FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of infections in patients supported with a continuous-flow LVAD.MethodsFrom a prospectively maintained database, we retrospectively analyzed the diagnostic performance of radiolabeled leucocyte scintigraphy and 18F-FDG PET/CT in 24 patients who had a LVAD with a suspected device-related infection. Both examinations were routinely performed in all patients. Infection was assessed by the International Society for Heart and Lung Transplantation criteria.ResultsTwenty-four patients were included: 15 had a specific VAD infection (5 cardiac-LVAD and 10 driveline), 6 had a VAD-related infection, while 3 patients had a non-VAD-related infection. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.2%, 66.7%, 95.2%, 66.7%, and 91.6%, respectively, for 18F-FDG-PET; and 71.4%, 100%, 100%, 33.3%, and 75%, respectively, for leucocyte scintigraphy. 18F-FDG PET/CT showed significantly higher sensitivity (P = 0.01) than leucocyte scintigraphy.Conclusion18F-FDG PET/CT and radiolabeled leucocyte scintigraphy single-photon emission computed tomography carry high performance in the diagnostic of LVAD infections. 18F-FDG PET/CT shows significantly higher sensitivity and could be proposed as first-line nuclear medicine procedure.Spanish AbstractAntecedentesEl uso de dispositivos de asistencia ventricular izquierda (DAVI) está incrementando en pacientes con insuficiencia cardiaca avanzada. Sin embargo, las infecciones relacionadas al dispositivo representan un reto diagnóstico y de tratamiento, con una importante tasa de morbilidad y mortalidad. El papel de los estudios de imagen de medicina nuclear en las infecciones de DAVI no se ha establecido claramente. El presente estudio comparó la precisión de la tomografía por emisión de positrones/tomografía computada con 18F-fluorodesoxiglucosa (18F-FDG PET/CT) y la gammagrafía con leucocitos marcados para el diagnóstico de infecciones en pacientes utilizando un DAVI de flujo continuo.MétodosDesde una base de datos obtenida de manera prospectiva, analizamos de manera retrospectiva el rendimiento diagnóstico de la gammagrafía de leucocitos marcados y del 18F-FDG PET/CT en 24 pacientes quienes tenían un DAVI con sospecha de infección relacionada al dispositivo. Ambos estudios fueron realizados rutinariamente en todos los pacientes. Se determinó la presencia de infección mediante los criterios de la ISHTL.ResultadosSe incluyeron veinticuatro pacientes, de los cuales 15 tuvieron una infección específica de DAV (5 con infecciones DAVI, y 10 con infección del driveline), 6 tuvieron una infección relacionada al DAV, y 3 pacientes tuvieron una infección no relacionada al DAV. La sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y precisión diagnóstica fueron 95.2%, 66.7%, 95.2%, 66.7% y 91.6%, respectivamente para 18F-FDG PET/CT, y 71.4%, 100%, 100%, 33.3% y 75%, respectivamente para la gammagrafía de leucocitos marcados. El 18F-FDG PET/CT mostró una significativa mayor sensibilidad (p=0.01) que la gammagrafía con leucocitos marcados.ConclusiónEl 18F-FDG PET/CT y la gammagrafía de leucocitos marcados tienen un alto desempeño en el diagnóstico de infecciones de DAVI. El 18F-FDG PET/CT muestra una significativa mayor sensibilidad y podría ser propuesto como el procedimiento de medicina nuclear de primera línea.Chinese Abstract背景左心室辅助装置 (LVAD) 越来越多的应用于重度心力衰竭患者。然而, 设备相关的感染有着重要的发病率和死亡率, 并且对其诊断和治疗均是一项挑战。对于 LVAD 相关感染, 核医学影像可扮演的角色一直没有完善。本研究针对装备有连续流式 LVAD 的感染病人,对比了 18F-FDG PET/CT 造影术和放射性标记白细胞闪烁扫描法对感染诊断的准确性。方法从一个前瞻性的数据库, 入选了24名疑似设备感染的 LVAD 病人, 并回顾性的分析了放射性标记白细胞闪烁扫描法和 18F-FDG PET/CT 的诊断表现。所有病人都常规进行了上述两种检查。利用 ISHLT 标准对感染情况进行评估。结果在入选的 24 名病人中, 15 名有明确的 VAD 感染 (5 名心脏的 LVAD 和 10 名动力传动系统装置), 6 名有 VAD 相关的感染,另外3名有 VAD 无关的感染。对于 18F-FDG PET/CT 诊断方法,其敏感性,特异性,阳性预测值,阴性预测值和准确率分别为: 95.2%, 66.7%, 95.2%, 66.7%, 和 91.6%; 而对于白细胞闪烁扫描诊断方法, 其敏感性, 特异性, 阳性预测值,阴性预测值和准确率分别为: 71.4%, 100%, 100%, 33.3% 和 75%。相比于白细胞闪烁扫描, 18F-FDG PET/CT 明显展现出较高的敏感性 (p=0.01)。结论18F-FDG PET/CT 和白细胞闪烁扫描 SPECT 对于 LVAD 感染的诊断具有很好的表现。18F-FDG PET/CT 展现出较高的敏感性,可以作为核医学的首要检查。French AbstractContexteL’utilisation du dispositif d’assistance ventriculaire gauche (DAVG) est en utilisation croissante chez les patients avec insuffisance cardiaque avancée. Cependant, les infections liées au dispositif sont un défi à reconnaître et à traiter en raison d’ un taux de morbidité et de mortalité important. Le rôle de l’imagerie de médecine nucléaire n’est pas encore bien établi pour les infections secondaires au DAVG. La présente étude compare la précision de la tomographie par émission de positrons / tomodensitométrie au 18F-fluorodéoxyglucose (18F-FDG TEP/TDM) et la scintigraphie leucocytaire radio-marquée pour le diagnostic d’infections chez des patients porteurs par un DAVG à flux continu.MéthodesA partir d’une base de données complétée de manière prospective nous avons analysé rétrospectivement les performances diagnostiques de la scintigraphie leucocytaire radio-marquée et de la TEP / TDM au 18F-FDG chez 24 patients ayant un DAVG avec une infection suspectée liée à l’appareillage. Les deux types d’examens scintigraphiques ont été systématiquement réalisé chez tous les patients. Le diagnostic d’infection fut établi selon les critères ISHLT.RésultatsParmi les 24 patients inclus, 15 avaient une infection spécifique de l’appareillage AVG (5 au niveau de la pompe et/ou canule d’insertion myocardique) et 10 au niveau du driveline, 6 avaient une infection indirectement liée à l’appareillage AVG, tandis que 3 patients avaient une infection non liée au DAVG. La sensibilité, la spécificité, la valeur prédictive positive, la valeur prédictive négative et la précision étaient de 95,2%, 66,7%, 95,2%, 66,7% et 91,6%, respectivement, pour le 18F-FDG-PET et 71,4%, 100%, 100%, 33,3 %, et 75%, respectivement, pour la scintigraphie leucocytaire. La TEP / TDM au 18F-FDG a montré une sensitivité significativement plus élevée (p = 0,01) que la scintigraphie leucocytaire.Conclusion18F-FDG TEP/TDM et scintigraphie leucocytaire radio-marquée SPECT s’avèrent très efficaces pour le diagnostic des infections à DVAG. La TEP/TDM au 18F-FDG montre une sensibilité significativement plus élevée et pourrait être proposée en tant que la procédure de médecine nucléaire de premier choix.

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score

Osteoporotic fractures associated with Cushings syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid‐treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual‐energy X‐ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS.

The impact of combination of regadenoson and isometric exercise on image quality of myocardial perfusion scintigraphy

Regadenoson (Rega) has become a well-established vasodilation agent to perform myocardial perfusion imaging (MPI) in patients unable to exercise. Its diagnostic performance is equivalent to adenosine, but with fewer side effects. Rega has been used off-label in symptom-limited stress protocols, with excellent safety and efficacy results. Rega has been combined with low-level exercise 4,5 or with maximal exercise associated to a submaximal heart rate response. In these settings, Rega does not increase the rate of adverse events, but it has a more favorable hemodynamic response and reduces the need for the use of aminophylline. Rega is preferably given during recovery rather than at peak exercise to avoid undesirable side effects. In a preliminary study, we demonstrated that adding a handgrip (HG) exercise to Rega is well tolerated and easily performed. In addition, there was also a nonsignificant trend toward better image quality (IQ). The aim of this study was to expand our preliminary results and assess whether the combination of HG and Rega improves IQ of MPI. We also examined the frequency of side effects and hemodynamic changes. METHODS

Hodgkin lymphoma: is there really a need for interim and end-of-treatment FDG-PET evaluations? – Response to Adams & Kwee

We thank our colleagues for their interest in and extensive evaluation of our article (Mesguich et al, 2016), which pointed out that, in Hodgkin lymphoma (HL), interim fluorodeoxyglucose positron emission tomography (FDG-PET) has a lower sensitivity than end-of-treatment PET (46 7% vs. 80%; P = 0 0078), i.e., a negative interim FDG-PET study cannot obviate the need for end-PET examination. We realize that this subject raises questions, and we tried to answer most of them in our article. However, Adams and Kwee stress some additional points that we will try to address. We restrict discussion to ABVD (adriamycin, bleomycin, vinblastine and dacarbazine)-treated patients, as in our report. The first point raised by Adams and Kwee is that we did not sufficiently address how these unsatisfactory results of interim FDG-PET evaluation should be interpreted for routine clinical management. They state that the sensitivity of 46 7% and the PPV of 43 8% seriously question whether interim FDG-PET results should be used for prognostication in this disease, and undermines the feasibility of FDG-PET adapted trials. We agree with Adams and Kwee that the sensitivity of interim PET is suboptimal. This calls for maintaining FDG-PET evaluation at the end of the treatment in order to identify patients who require further therapy (Mesguich et al, 2016). Our results are in agreement with findings from recent trials in advanced HL patients (Johnson et al, 2016; Press et al, 2016), which showed that the relapse rates in interim-PET-negative patients are higher than previously thought (Gallamini et al, 2014). Unfortunately, results from end-of-chemotherapy PET are not available in these reports (Johnson et al, 2016; Press et al, 2016). Despite the limited sensitivity of interim PET, early identification of some patients with resistance to therapy is an important issue, particularly in patients with advanced HL. The positive predictive value of interim PET varies with disease stage and risk factors. A recent retrospective analysis found that 3-year progression-free survival (PFS) rates in interim PET-positive patients ranged between 76 9% and 20% depending on initial risk group (Oki et al, 2014). A retrospective multicentre study found a 3-year PFS rate of 28% for patients with advanced HL and positive interim PET (Gallamini et al, 2014). Based on these results, prospective multicentre trials of PET-adapted therapy have found it unethical to randomise advanced HL patients with positive interim PET after two cycles of ABVD; all these patients were switched to intensified regimens (Johnson et al, 2016; Press et al, 2016). These trials showed encouraging PFS rates in patients offered escalated therapy. We, however, agree with Adams and Kwee that, in the absence of randomisation, the positive predictive value cannot be assessed from these trials (Johnson et al, 2016; Press et al, 2016). Adams and Kwee question why the sensitivity of FDGPET was higher at end of treatment than at interim analysis. Indeed, six patients who were interim PET negative showed FDG-avid lesions on end-of-treatment PET, which might be the result of different reasons. Some tumours might initially respond to chemotherapy but refractory clones are selected that show late resurgence. Also, interim PET is performed shortly after a chemotherapy cycle (e.g. c. 10 days after the second cycle). With this short timing there might be a ‘stunning effect’. In contrast, end-of-treatment PET is usually performed 6–8 weeks after the end of therapy. Finally, for interim PET we used liver as reference (Deauville score ≥4 is positive) based on Lugano guidelines (Cheson et al, 2014), while for end-of-treatment we used mediastinal blood pool (Deauville score ≥3 is positive), the traditional reference region for end-of-treatment PET interpretation (Juweid et al, 2007). Indeed, current guidelines are unclear whether a Deauville score of 3 on end-of-treatment PET should be considered negative or positive (Cheson et al, 2014). This has received little prospective evaluation and validation. We agree with Adams and Kwee that prospective studies can be of importance to define the optimal criteria for end-of-treatment PET positivity (>mediastinal blood pool or >liver). The sensitivity of end-of-treatment FDG-PET in our series (80%) is within the range (50–100%) reported in a metaanalysis (Terasawa et al, 2008). Our findings on superiority of end-PET are in agreement with those from Barnes et al (2011). Our reading of this paper (Barnes et al 2011) could not find the figures quoted in the table presented by Adams and Kwee. Finally, Adams and Kwee state that it might not be at all helpful to assess response to chemotherapy in HL patients, whether by interim or end-of-treatment evaluations. They raised the fact that HL is a highly curable disease and that the number of end-of-treatment FDG-PET scans required to detect one case with residual disease is very high. They also Correspondence

Response to the letter by Adams and Kwee, entitled: “Unproven value of end-of-treatment FDG-PET in Hodgkin lymphoma”

Sir, We thank Drs. Adams and Kwee for their interest in our recent editorial on patients with advanced Hodgkin’s lymphoma (HL), i.e. stages III/IV and stage IIB with unfavourable features [1]. These patients are often treated with six to eight cycles of ABVD chemotherapy, but have a 30–35% relapse rate [2]. Their clinical situation is different from that of patients with early-stage favourable disease, who have a very high cure rate when treated with combined modalities as first-line treatment (two or three cycles of ABVD followed by radiotherapy) [2]. Escalated BEACOPP as first-line therapy is associated with higher cure rates than ABVD in patients with advancedHL, but also with higher rates of short-term and long-term adverse effects (haematological toxicity, infections, infertility, secondary malignancies) [3]. In patients with advanced HL treated with ABVD we suggested that end-oftreatment PET should be retained, as in some patients it can reveal treatment failure missed by interim FDG PET (performed after two cycles of ABVD). Adams and Kwee argue that there is no role for either interim or end-of-treatment FDG PET in HL [4]. Their opinion letter is an interesting contribution to the debate. It is, however, based on carefully chosen data, equally carefully chosen omissions, and some circular reasoning. They also mix up different clinical realities. In our editorial, we made clear that interim FDG PET, although it may identify some patients with refractory disease at an early stage, has onlymoderate sensitivity [1]. Adams and Kwee add that Ba recently published, prospective large-scale study including 1100 patients with advanced-stage Hodgkin lymphoma reported interim FDG-PET to have no value at all in predicting prognosis^. In the HD18 trial by Borchmann and colleagues the 3-year progression-free survival exceeded 90% in patients positive on interim PET [5]. However, Adams and Kwee fail to mention three important details about this study: (1) patients were treated with eight cycles of escalated BEACOPP, (2) the threshold used for positivity on interim PETwas quite low (uptake higher than that of the mediastinal blood pool), so that 40% of patients were classified as positive on interim PET, and most importantly (3) end-ofchemotherapy FDG PET was used to decide whether radiotherapy was needed in patients with a residual mass (>2.5 cm) as previously done in the HD15 trial [6]. Thus, out of 440 patients positive on interim PET, 168 received consolidation with 30-Gy radiotherapy at the end of chemotherapy [5]. Because the study based its interventional strategy on FDG PET, it cannot be used to assess the prognostic value of FDG PET itself. Adams and Kwee believe that Bthere is no role for end-oftreatment FDG-PET in HL either^, because Bin order to justify end-of-treatment FDG-PET, 4 needs have to be met: (1) endof-treatment FDG-PET needs to be sensitive, (2) end-oftreatment FDG-PET has to be specific in order to prevent overtreatment of patients without residual disease after initial therapy, (3) early detection of residual disease at end-oftreatment FDG-PET before the onset of symptomatic disease and early initiation of salvage treatment must result in a benefit in outcome in terms of overall survival, and (4) this This reply refers to the letter to the editor at doi:10.1007/s00259-0173771-8.