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This single‐arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)‐guided therapy for newly diagnosed advanced‐stage classic Hodgkin lymphoma (cHL). Patients aged 16–60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five‐point Deauville scale. PET2‐negative patients continued an additional four cycles of ABVD, whereas PET2‐positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co‐primary endpoints were 2‐year progression‐free survival (PFS) among all eligible and PET2‐positive patients. Ninety‐three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28–48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2‐positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2‐negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow‐up period of 41.1 months, the 2‐year PFS of 92 eligible patients and 19 PET2‐positive patients were 84.8% (80% confidence interval [CI], 79.2–88.9) and 84.2% (80% CI, 69.7–92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET‐guided therapy is a useful treatment option for younger patients with newly diagnosed advanced‐stage cHL. Registration number: jRCTs031180218. JCOG1305 demonstrated that interim PET‐guided therapy was useful for younger patients with newly diagnosed advanced‐stage cHL.

Purpose The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. Methods From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. Results Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % ( p  = 0.001) and 44 % vs. 79 % ( p  < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 ( p  = 0.0005, RR 6.3) and TMTV0 ( p  < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml ( n  = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml ( n  = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml ( n  = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % ( p  < 0.0001), respectively. Conclusion TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare, aggressive lymphoma affecting young adults. Interim PET/CT (iPET/CT) scans are used to assess treatment response, but the positive predictive value of standard Deauville score remains limited. This retrospective multicenter study analyzed 116 PMBCL patients treated with anthracycline-based chemoimmunotherapy, focusing on 90 patients with high quality iPET/CT. Semiquantitative radiomics metrics, including changes in maximum standardized uptake value (dSUVmax), metabolic tumor volume (dMTV), and total lesion glycolysis (dTLG), were assessed alongside event-free survival (EFS). All interim and final PET/CT scans were independently reviewed by two nuclear medicine physicians blinded to outcomes. Among the 90 patients, 62 (68.9%) were iPET-positive (Deauville scores 4–5). Event-free survival (EFS) at 3 years was significantly higher in iPET-negative patients compared to iPET-positive patients (75% vs. 29%; p  < 0.01). Radiomics analysis demonstrated that dSUVmax, dMTV, and dTLG provided superior predictive accuracy for EFS. Values below optimized cut-off thresholds demonstrated significantly better outcomes (e.g., 3-y EFS: 77.8% for dSUVmax ≥ 80% vs. 11.1% for dSUVmax < 80%, p  < 0.01). Radiomics-based metrics outperformed visual iPET/CT assessment in identifying high-risk patients, underscoring their potential in guiding treatment. Future research should integrate radiomics with clinical factors to enhance PET-guided treatment strategies.

Hodgkin lymphoma (HL), a disease of mostly young patients, also peaks in the elderly. Despite the profound improvement in the outcome of young patients, in the elderly, 5-year progression-free survival (PFS) rates are under 70%. Interim PET-CT (iPET) is known to be highly predictive for PFS in young HL patients, but it has not been sufficiently validated in the elderly patient population. In this multi-center collaboration, all consecutive elderly patients (age ≥ 60) diagnosed with HL between 1998 and 2016 were retrospectively reviewed. Baseline characteristics, outcome measures, and iPET results, classified according to the Deauville score, were recorded and analyzed. We identified 78 elderly HL patients (median age 69) who underwent iPET. ABVD was the treatment regimen in 52 (67%) patients. Eighty-three percent of patients had iPET scores of 1–3 while 17% had scores of 4–5. Patients with iPET scores of 1–3 had 5-year PFS and OS rates of 72% and 82% compared with 25% and 45%, respectively, in patients with scores of 4–5 (p < 0.001). Our findings show that iPET is highly predictive of outcome in elderly HL patients and provide evidence that iPET-guided therapy in this patient population may be key to achieving superior treatment outcome.

Objective Interim 18 F-FDG PET/CT (iPET/CT) imaging demonstrates potential in assessing the early therapeutic response in lymphoma. Nevertheless, the prognostic significance of interim PET-CT in diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate whether semi-quantitative PET/CT metabolic parameters and other metrics could enhance the prognostic value of interim PET/CT in DLBCL patients exhibiting partial metabolic remission (PMR). Methods A retrospective analysis was performed from January 2018 to December 2023, focusing on patients with DLBCL who achieved PMR on interim PET-CT. Patient demographics, clinical characteristics, and semi-quantitative PET/CT metabolic parameters were extracted from the medical records. Multivariate analyses were conducted to identify the risk factors associated with failure to achieve complete metabolic remission (CMR) at the end of treatment (EOT). Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cut-off values for continuous predictive variables. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods, and risk factors were evaluated using Cox regression models. Results In a cohort consisting of 80 newly diagnosed DLBCL cases that exhibited PMR on interim PET scans, 50 cases ultimately achieved CMR, while the remaining 30 cases still had positive PET findings at EOT. Analysis revealed that the interim lesion-to-liver maximum standardized uptake value ratio (RLL) and bone marrow involvement were independent prognostic factors for positive PET-CT outcomes at EOT. Notably, an interim RLL threshold greater than 1.66 emerged as a reliable predictor with a sensitivity of 73.3% and a specificity of 72.0%. Additionally, the International Prognostic Index (IPI) and interim RLL were identified as independent prognostic indicators for both progression-free survival (PFS) and overall survival (OS). Conclusion Our study revealed that within the cohort of DLBCL patients exhibiting PMR on interim PET scans, an interim RLL greater than 1.66 and bone marrow involvement emerged as independent risk factors for positive PET results at the end of treatment. Additionally, the IPI and interim RLL were identified as independent prognostic markers for both progression-free survival and overall survival. The integration of clinical characteristics with semi-quantitative PET/CT parameters has the potential to enhance the prognostic role of interim PET/CT exhibiting PMR in DLBCL cases.

The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the introduction of the international prognostic scoring (IPS) system; therapeutic decision-making based on both IPS and interim PET/CT data; the finding that a negative interim PET/CT result could be safely used for treatment de-escalation; the introduction of intensive combination chemotherapy like escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone); and further modification of this protocol with the incorporation of a conjugated anti-CD30 antibody brentuximab vedotin (BV) into first-line regimens, like BV-AVD (BV+ adriamycin, vinblastine and dacarbazine) and BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone). The accruing data about the toxicity of the escalated BEACOPP protocol have led to decreasing the number of therapeutic cycles, substitution of toxic agents like procarbazine with dacarbazine (e.g., BEACOPDac), and reduction/omission of radiation therapy. Lately, a significant advancement has been made by the integration of checkpoint inhibitors in the first-line treatment, with preliminary results demonstrating the superiority of anti-PD1 combined with chemotherapy (nivolumab-AVD) compared to the BV-AVD regimen. This review aims to analyze recently published studies whose findings could change the treatment practice in advanced-stage HL.

Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along with the main PET-driven trials for therapeutic decisions. The emergence of total metabolic tumor volume as a new functional prognostic factor will also be discussed.

Recent advances in lymphoma treatment have significantly improved the survival of patients; however, the current approaches also have varying side effects. To overcome these, it is critical to implement individualized treatment according to the patient’s condition. Therefore, the early identification of high-risk groups and targeted treatment are important strategies for prolonging the survival time and improving the quality of life of patients. Interim positron emission tomography-computed tomography (PET-CT) has a high prognostic value, which can reflect chemosensitivity and identify patients for whom treatment may fail under this regimen. To date, many prospective clinical studies on interim PET (iPET)-adapted therapy have been conducted. In this review, we focus on the treatment strategies entailed in these studies, as well as the means and timing of iPET assessment, with the aim of exploring the efficacy and existing issues regarding iPET-adapted treatment. It is expected that the improved use of PET-CT examination can facilitate treatment decision-making to identify precise treatment options.

Background/Aim: The present study retrospectively investigated the predictive accuracy of interim positron emission tomography/computed tomography (iPET/CT) based on the Deauville 5-point scale (5-PS) and a quantitative SUV-based assessment in patients with extranodal (EN) diffuse large B cell lymphoma (DLBCL). Patients and Methods: The Deauville 5-PS and the SUVmax reduction (ΔSUVmax) assessment for interpreting the response to iPET/CT were used. Results: A total of 163 patients were enrolled in this study. With a median follow-up of 52.5 months, ΔSUVmax successfully predicted the survival outcomes of patients with one extranodal (EN) involvement in terms of overall survival (OS) (p=0.012) and progression-free survival (PFS) (p<0.001). Visual assessment using the Deauville 5-PS did not predict survival outcomes in patients with one or more EN involvements in terms of OS and PFS. Conclusion: The quantitative SUV-based assessment with iPET/CT was a significant prognosticator for long-term survival outcomes, especially in patients with one EN involvement.

Treating patients with DLBCL remains a challenge, as the response to first-line immunochemotherapy is somewhat unpredictable. The International Prognostic Index (IPI) is one of the most widely used methods for assessing prognosis. Interim PET/CT (iPET/CT) can play an important role in the early identification of ‘non-responder’ patients before the end of treatment examination. In this study, we retrospectively analyzed 104 newly diagnosed DLBCL patients treated with R-CHOP-like regimens who underwent iPET/CT imaging during therapy. There was a significant difference in 2-year OS between patients with negative iPET/CT and those with positive iPET/CT. Patients who had positive iPET/CT showed inferior 2-year PFS compared to those with negative iPET/CT. According to IPI, there was a statistically significant difference in 2-year OS and PFS between patients in the lower and higher risk groups. However, these patients can be further subdivided according to iPET/CT. The iPET/CT results in the present study clearly separate good- and poor-prognosis patients according to differences in 2-year OS, both in the lower and higher IPI risk groups. These results are in agreement with those of previous studies that demonstrated that iPET/CT has high negative predictive value, clearly identifying good-prognosis patients even within the poor-prognosis IPI group.