Our objective was to assess the prognostic value of ¹⁸F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim ¹⁸F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2–3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%–83%) for event-free survival (EFS) and 86% (95% CI, 81%–89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET–negative, and 117 (36%) were I-PET–positive. Two-year EFS was 90% (95% CI, 85%–93%) for I-PET–negative and 58% (95% CI, 48%–66%) for I-PET–positive, with a hazard ratio of 5.31 (95% CI, 3.29–8.56). Two-year OS was 93% (95% CI, 88%–96%) for I-PET–negative and 72% (95% CI, 63%–80%) for I-PET–positive, with a hazard ratio of 3.86 (95% CI, 2.12–7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%–98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%–100%). In contrast, the 107 I-PET–positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%–93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%–48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.

Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. Methods: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. Results: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%–86%) for event-free survival (EFS) and 88% (83%–91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%–89%) for EFS and 88% (77%–94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%–95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%–64%) for EFS and 55% (32%–73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48–4.79) for EFS and 3.94 (1.93–8.06) for OS. Conclusion: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow ¹⁸F-FDG uptake identified on the staging PET scan. Abnormal ¹⁸F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.

Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4–10 ng/mL. All patients underwent PET/CT scanning with ⁶⁸Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment (P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR. Visual Abstract

Purpose To assess the cost effectiveness of fluorine-18–fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with Hodgkin's lymphoma (HL) with unconfirmed complete remission (CRu) ...