Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the investigator-sponsored randomized phase II NIVAHL trial for early-stage unfavorable classical Hodgkin lymphoma (HL), two schedules of four cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine followed by 30 Gy involved-site radiotherapy resulted in high complete remission rates and an unprecedented 1-year progression-free survival in 109 patients. In this article, we report the preplanned final analysis conducted three years after the registration of the last patient including long-term safety results. No survival events were observed since the primary analysis, and after a median follow-up (FU) of 41 months, the overall survival was 100% in both treatment groups. The progression-free survival was 98% and 100% in the sequential and concomitant nivolumab, doxorubicin, vinblastine, and dacarbazine treatment groups, respectively. At last FU, the mean forced expiratory pressure in one second was 95.5% (standard deviation 12.7%), the mean diffusion capacity for carbon monoxide adjusted for hemoglobin was 82.8% (standard deviation 15.4%), and the left ventricular ejection fraction was in the normal range in 95% of patients. Hypothyroidism requiring long-term medication occurred in 15% of patients, who were nearly exclusively female (87%). No second primary malignancies occurred, and no patient required corticosteroid treatment at last FU. Patient-reported normalized global quality-of-life score measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 improved over time. This preplanned FU analysis of the largest anti–programmed death protein 1 HL first-line trial to date confirms the outstanding efficacy and relatively favorable safety profile of this therapeutic approach.

Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning is performed during staging. Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% (95% confidence interval: 99.2-100%) with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% confidence interval: 75.1-99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. As compared to BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. The trials included in this analysis were registered at ClinicalTrials.gov: HD16 - NCT00736320, HD17 - NCT01356680, HD18 - NCT00515554.

The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both ¹⁸F-FDG and 3′-deoxy-3′-¹⁸F-fluorothymidine (¹⁸F-FLT) in patients with advanced non–small cell lung cancer. Methods: Data were used from a prospective trial involving patients with untreated stage IV non–small cell lung cancer. ¹⁸F-FDG PET and ¹⁸F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV_max], 2-dimensional peak SUV [SUV_2Dpeak], 3-dimensional [3D] peak SUV [SUV_3Dpeak], 3D isocontour at 50% of the maximum pixel value [SUV₅₀], 3D isocontour at 50% adapted for background [SUV_A50], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV_A41], 3D isocontour at 70% of the maximum pixel value [SUV₇₀], 3D isocontour at 70% adapted for background [SUV_A70], and relative SUV threshold level [SUV_RTL]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan–Meier statistics and a log-rank test. Results: Patients with a metabolic response on early ¹⁸F-FDG PET and ¹⁸F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV_max, SUV₅₀, SUV_A50, and SUV_A41. Patients with a metabolic response measured by SUV_max and SUV_3Dpeak on late ¹⁸F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan–Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early ¹⁸F-FLT or in late ¹⁸F-FDG. Conclusion: Early ¹⁸F-FDG PET and ¹⁸F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV_max, SUV₅₀, SUV_A50, and SUV_A41 measured with ¹⁸F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early ¹⁸F-FLT PET and late ¹⁸F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non–small cell lung cancer treated with erlotinib.

Purpose: Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT).Patients and Methods: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression.Results: In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P = .022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P = .9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%).Conclusion: Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.

Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology—both imaging hardware and reconstruction software—into clinical care, we now find ourselves in a transition period in which traditional and new technologies coexist. The effects on the clinical value of PET imaging and its interpretation in routine clinical practice require careful reevaluation. In this review, we provide a comprehensive summary of important factors influencing quantification and interpretation with a focus on recent developments in PET technology. Finally, we discuss the relationship between quantitative accuracy and subjective image interpretation.