Purpose Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET) –computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. Methods An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. Results A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. Conclusion This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.

PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL.

Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL.

© F e r r a t a S t o r t i F o u n d a t i o ncomparable, with different timing of the interim PET during the course of treatment and differing PET methodologies. Most studies used stand-alone PET, which has now been replaced by PET-CT. Reporting methods were not consistent making it difficult to judge how these results should be applied in clinical practice.In 2009 an international meeting attended by hematologists and nuclear medicine specialists was held in Deauville, France, with the intention of defining simple and reproducible criteria for interim-PET reporting in lymphoma.11 A five-point scale (5-PS) developed at Guy's and St. Thomas' Hospital in London was adopted 12 as the "Deauville criteria". An international study was launched to compare previous reports on the accuracy of interim PET in predicting treatment outcome in Hodgkin lymphoma with an international cohort of patients scanned using PET-CT after two cycles of ABVD and to evaluate the reproducibility of the 5-PS among reporters. The criteria for enrollment, the breakdown of patients according to stage (early unfavorable and advanced-stage) and the endpoints were the same as in the JID. Methods Retrieval of patients' dataConsecutive patients affected by Hodgkin lymphoma from participating centers worldwide diagnosed between January 2002 and December 2009 were retrospectively enrolled with the following inclusion criteria: (i) stage IIB to stage IVB or stage IIA Hodgkin lymphoma with adverse prognostic factors (at least three nodal sites involved, sub-diaphragmatic presentation, bulky disease, and erythrocyte sedimentation rate > 40 mm/h); (ii) treatment with four to eight cycles of ABVD with or without involved-field radiotherapy or consolidation radiotherapy; (iii) staging with PET/CT at baseline and after two courses of ABVD (PET-0 and PET-2, respectively); (iv) no change to treatment based on interim-PET results; and (v) a minimum follow-up of 1 year after completion of firstline treatment. Patients escalated to salvage treatment during ABVD chemotherapy were eligible only if the treatment change was based on clinical and/or radiological evidence of disease progression/resistance.The study was approved by the ethical committee of the coordinating center in Cuneo (Italy) and conducted according to the Helsinki declaration. Specific informed written consent was not required as all data were retrospectively collected in an anonymized format, in agreement with specific institutional and national requirements. AG, SC and ER analyzed the data and all co-authors had access to the primary data.Clinical data on 400 patients were collected; however only 335 paired scans (baseline and interim) were available for review. Of these, 75 were then excluded because there were no CT data (n=21), no baseline PET (n=25), no interim PET (n=1), missing CT slices (n=3), missing PET slices (n=10), poor quality PET images (n=6) or miscellaneous reasons (n=9). Complete data from 260 patients were available for analysis from 17 international academic institut...

At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. Methods: A cohort of advancedstage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Results: Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were falsepositive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P , 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf a. Conclusion: The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.Key Words: interim PET; Hodgkin lymphoma; interpretation criteria; concordance rate; clinical trial Nucl Med 2013; 54:683-690 DOI: 10.2967/jnumed.112.110890 Prel iminary reports have shown that 18 F-FDG PET performed early during doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) treatment of patients with Hodgkin lymphoma predicts the treatment outcome (1,2). Moreover, interim PET is a more effective predictor of treatment response than well-established clinical prognostic factors such as the International Prognostic Score (3). Further reports have confirmed these findings, with an overall sensitivit...

Although the Deauville criteria are valid for assessing the prognostic value of early PET/CT in DLBCL, computation of the ΔSUVmax leads to better performance and interobserver reproducibility, and should be preferred when a baseline scan is available.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

SummaryInterim 2-[18F]Fluoro-2-deoxy-D-glucose Positron Emission Tomography performed after two chemotherapy cycles (PET-2) is the most reliable predictor of treatment outcome in ABVD-treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET-2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET-2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34 months (12-52) the 2-year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET-2 positive and 92% for PET-2 negative patients. For 154 patients in which treatment was correctly given according to PET-2 review, the 2-year FFS was 91%: 62% for PET-2 positive and 95% for PET-2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET-2 positive patients, showed better results than ABVD-treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747).