End of induction [18F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis.

It is well established that some patients with diffuse large B-cell lymphoma (DLBCL) and the negative end of treatment PET-CT (EOT-PET-CT) will relapse, while a proportion with positive uptake can still obtain long-term EFS. We reviewed data of 200 consecutive, previously untreated patients with DLBCL recorded in Italy and Israel between 2007 and 2015. We found that patients with negative EOT-PET-CT with AMC > 630/mmc have a 3-years EFS of 72%, compared to those with AMC ≤ 630/mmc that have an EFS of 84%. Furthermore, considering patients with positive EOT-PET-CT, those with AMC > 630/mmc have a 3-years EFS of 8%, while those with AMC ≤ 630/mmc have an EFS of 38%. Thus, it appears that combining the gold standard for response evaluation EOT-PET-CT with a simple and inexpensive parameter like AMC at diagnosis, further improves prognostication in DLBCL. Applying this simple method can be useful for all doctors working in lymphoma clinical practice.

Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma.

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Primary Sarcomatoid Carcinoma of the Lung: Radiometabolic ((18)F-FDG PET/CT) Findings and Correlation with Clinico-Pathological and Survival Results.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a very rare and uninvestigated subtype of non-small cell lung cancer (NSCLC). METHODS: The aims of this study were to define the radiometabolic features (by (18)F-FDG PET/CT) in a bi-centric cohort of 49 PSC patients and to explore their relation with clinico-pathological characteristics and long-term survival results after surgical treatment. RESULTS: There were 40 males and 9 females aged 65.2 ± 10.47 years. Overall long-term survival was 26.7 % at 5 years. Mean and median values of SUVmax were 15.21 and 15, respectively (SD ±5.5). Performing an age-, gender- and staging-matched analysis comparing PSC Stage-I only with a cohort of Stage-I NSCLC (n = 93), we observed significantly higher SUVmax values in PSC group (15.11 vs 7.66, p = 0.001). CONCLUSIONS: No differences in terms of SUVmax were found with regard to tumour dimensions, histology (pure vs mixed, pleomorphic vs others), pathological stage and pattern of recurrence. P-stage, surgical radicality, vascular/lymphatic invasion but not SUVmax affected long-term survival in PSC.

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Prognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies.

BACKGROUND: The value of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET) imaging in response assessment after first-line rituximab chemotherapy for follicular lymphoma has been documented. We analysed the application of the five-point Deauville scale (5PS; used to score FDG uptake on PET images) in a large cohort derived from three studies, to assess the correlation between post-induction PET status and survival in patients with follicular lymphoma. METHODS: In this pooled analysis, we used data from three multicentre prospective studies of first-line rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma (the PRIMA study, the PET-Folliculaire study, and the Fondazione Italiana Linfomi FOLL05 study). Patients included in this analysis received at least six cycles of rituximab and chemotherapy before response assessment with conventional contrast-enhanced CT and PET low-dose CT (PET). We included only patients who had a PET scan within 3 months of the last dose of induction rituximab. Patient data, including conventional CT-based response assessment, were recorded for all patients undergoing PET review. Scans undergoing central PET review were scored independently by three reviewers according to the 5PS. The primary endpoints were progression-free survival and overall survival according to the 5PS score of post-induction PET scan (ie, positive [≥4 points] or negative [<4 points]), analysed in the central review population. FINDINGS: Between Dec 24, 2004, and Sept 22, 2010, 439 of the patients enrolled in the three studies underwent local PET assessment, 246 of whom had centrally reviewed post-induction scans. 41 (17%) of 246 patients had a positive post-induction PET scan according to a cutoff of 4 or higher on the 5PS, with substantial reporter concordance. With a median follow-up of 54·8 months (IQR 39·7-68·5; range 7·7-90·1), the hazard ratio (HR) for progression-free survival for patients with a positive PET scan versus those with a negative PET scan was 3·9 (95% CI 2·5-5·9; p<0·0001), and for overall survival was 6·7 (2·4-18·5; p=0·0002). For patients with a positive PET scan, 23·2% (95% CI 11·1-37·9) of patients were progression free at 4 years compared with 63·4% (55·9-70·0) of those who had a negative PET scan (p<0·0001); 4-year overall survival was 87·2% (95% CI 71·9-94·5) versus 97·1% (93·2-98·8), respectively (p<0·0001). Conventional CT-based response (ie, complete response or unconfirmed complete response vs partial response) was weakly predictive of progression-free survival (HR 1·7 [95% CI 1·1-2·5]; p=0·017). INTERPRETATION: PET-CT rather than contrast-enhanced CT scanning should be considered as a new standard for response assessment of follicular lymphoma in clinical practice, and could help guide response-adapted therapy. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health.

Integrated FDG-PET/CT imaging is useful in the approach to carcinoid tumors of the lung.

BACKGROUND: Carcinoids enter the differential diagnosis of the solitary pulmonary nodule. Bronchial carcinoids have been traditionally considered as FDG-PET negative but recent studies have found an higher sensitivity of integrated FDG-PET/CT for the detection of these neoplasms. The purpose of this study was to investigate the value of integrated FDG-PET/CT for the evaluation of SPN suspected to be carcinoids. METHODS: All patients with pathologically proven bronchial carcinoids who had FDG-PET/CT scans between 2006 and 2012 have been retrospectively reviewed. PET/CT was performed with the same scanner and the same technique for all patients. The following data were retrieved: age, sex CT findings (side, location, size, shape, margins), SUVmax, type of operation, pathological findings (size and number of mitoses). Regarding PET findings, only SUVmax was considered, whereas the visual assessment was not undertaken. Carcinoids were defined as typical and atypical and as central and peripheral. The long-term follow-up was also recorded. The SUVmax was compared with the other clinical, radiological and pathological variables to find any significant difference or correlation. RESULTS: Twenty-five patients were retrieved, 24 typical and one atypical carcinoid, 21 peripheral and 4 central lesions. The mean diameter on CT-scan was 25.3 mm and the clinical size correlated well with the pathological size. Sixty percent of the tumors were ovoid and 68% had smooth margins. The mean SUVmax was 3.6 (range 1.4-12.9). All the lesions were completely resected. The regression analysis showed a direct correlation between the SUVmax and the tumor size (p = 0.004). No further correlations were found between the SUVmax and the other variables. None of the patients had recurrent disease or died during the follow-up. CONCLUSIONS: Our study showed that FDG-PET/CT might be a useful tool in the evaluation of SPNs suspected to be bronchial carcinoids. When a solitary pulmonary nodule shows an ovoid/round shape and smooth margins on the CT scan and demonstrates an FDG uptake higher than that of the normal lung and with a SUVmax value >1-1.5, a carcinoid should be suspected. If benign lesions can be presumably excluded, surgical resection or at least a biopsy of the lesion is recommended.

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma.

PURPOSE: To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. METHODS: Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). RESULTS: There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. CONCLUSION: The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.